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Ratajczak-Pawłowska AE, Michalak M, Szymczak-Tomczak A, Rychter AM, Zawada A, Skoracka K, Dobrowolska A, Krela-Kaźmierczak I. Is There Any Association Between Fat Body Mass and Bone Mineral Density in Patients with Crohn's Disease and Ulcerative Colitis? Nutrients 2025; 17:466. [PMID: 39940324 PMCID: PMC11820439 DOI: 10.3390/nu17030466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 01/22/2025] [Accepted: 01/24/2025] [Indexed: 02/16/2025] Open
Abstract
Background: The study aimed to investigate the association between fat body mass and bone mineral density (BMD) of the lumbar spine (L1-L4), femoral neck, and total body. Methods: We studied 95 patients with Crohn's disease (CD), 68 with ulcerative colitis (UC), and 40 healthy adults (control group-CG) aged 18-50 years old. The BMD of lumbar spine and femoral neck was assessed as well as body composition. Results: A lower fat mass percentage was observed in about 8% of CD, 13% of UC, and 3% of CG. An increased percentage of fat mass was common, and occurred above 50% of CD, 40% of UC, and about 60% of CG. Body fat mass and fat mass percentage were significantly lower among UC compared with the CG (p-value < 0.001) and CD (p-value < 0.01) in women. Body fat mass correlated positively with the BMD and T-score of L1-L4 and total body mass in men with UC. We found a positive correlation between the fat body mass and BMD and T-score of L1-L4, femoral neck, and total body in women with IBD. Among CG, positive correlations occurred between the fat body mass and BMD of L1-L4, BMD of total body, and T-score of total body, but only in men. CRP (C-reactive protein) correlated negatively with fat body mass only in men with CD. Conclusions: A higher fat mass percentage is common among IBD patients and healthy adults despite a normal body mass index. Body fat mass is a predictor of nutritional status and likely influences the course of the disease, as it correlated positively with BMD, T-score, and Z-score. The association between fat tissue and bone health appears to be stronger in women. Further studies are needed to investigate additional factors that may affect bone health in IBD.
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Affiliation(s)
- Alicja Ewa Ratajczak-Pawłowska
- Laboratory of Nutrigenetics, Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland;
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (A.S.-T.); (A.Z.); (K.S.); (A.D.)
| | - Michał Michalak
- Department of Computer Science and Statistics, Poznan University of Medical Sciences, 61-701 Poznan, Poland;
| | - Aleksandra Szymczak-Tomczak
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (A.S.-T.); (A.Z.); (K.S.); (A.D.)
| | - Anna Maria Rychter
- Laboratory of Nutrigenetics, Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland;
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (A.S.-T.); (A.Z.); (K.S.); (A.D.)
| | - Agnieszka Zawada
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (A.S.-T.); (A.Z.); (K.S.); (A.D.)
| | - Kinga Skoracka
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (A.S.-T.); (A.Z.); (K.S.); (A.D.)
- Doctoral School, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Agnieszka Dobrowolska
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (A.S.-T.); (A.Z.); (K.S.); (A.D.)
| | - Iwona Krela-Kaźmierczak
- Laboratory of Nutrigenetics, Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland;
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (A.S.-T.); (A.Z.); (K.S.); (A.D.)
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Tarancon-Diez L, Iriarte-Gahete M, Sanchez-Mingo P, Muñoz-Fernandez MÁ, Navarro-Gomez ML, Pacheco YM, Leal M. Impact of obesity on iron metabolism and the effect of intravenous iron supplementation in obese patients with absolute iron deficiency. Sci Rep 2025; 15:1343. [PMID: 39779726 PMCID: PMC11711491 DOI: 10.1038/s41598-024-84498-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 12/24/2024] [Indexed: 01/11/2025] Open
Abstract
Obesity and iron deficiency (ID) are widespread health issues, with subclinical inflammation in obesity potentially contributing to ID through unclear mechanisms. The aim of the present work was to elucidate how obesity-associated inflammation disturb iron metabolism and to investigate the effect of intravenous (IV) iron supplementation on absolute iron deficient pre-obese (BMI 25.0-29.9 kg/m2) and obese (BMI > 30 kg/m2) individuals compared to healthy weight (HW) group (BMI 18.5-24.9 kg/m2). Iron-related, hematological and inflammatory biomarkers along with erythropoietin (EPO) were studied based on body mass index (BMI) in a Spanish cohort of non-anemic participants (n = 721; 67% women; median age of 48 years [IQR: 39-57]) and in a subgroup of subjects (n = 110) with absolute ID (ferritin < 50 ng/mL) after completing an IV iron therapy. Obese group exhibited higher levels of ferritin, hemoglobin (Hb), soluble transferrin receptor (sTfR) and hepcidin compared to HW group. Elevated BMI was independently associated with increased sTfR levels. While no statistical differences were found in EPO among groups, obese showed increased levels that inversely correlated with Hb only in pre-obese and obese groups. IV iron therapy on obese participants had significant improvements on iron-related parameters and Hb levels. Notable obesity-associated disturbances in iron metabolism are described and indicate a mixed ID among both, women and men. These findings highlight the importance of tailored interventions to correctly address ID in obese population.
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Grants
- CB21/13/00077 Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
- CB21/13/00077 Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
- CP23/00009 Instituto de Salud Carlos III (ISCIII) through the Miguel Servet Program, Madrid, Spain
- CM22/00198 Instituto de Salud Carlos III (ISCIII) through the Río Hortega Program, Madrid, Spain
- CB22/01/00041 Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBERBBN), Madrid, Spain
- PI21/00357 Fondo de Investigación Sanitaria, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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Affiliation(s)
- Laura Tarancon-Diez
- Grupo de Infecciones en la Población Pediátrica, Health Research Institute Gregorio Marañón (IiSGM), Calle Dr. Esquerdo 46, 28007, Madrid, Spain.
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBER-INFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
| | - Marianela Iriarte-Gahete
- Immunology Service, Unit of Clinical Laboratories, Institute of Biomedicine of Seville, IBiS / Virgen del Rocío University Hospital / CSIC / University of Seville, Seville, Spain
| | - Pilar Sanchez-Mingo
- Synlab Global Diagnosis, Hospital Viamed Santa Ángela de La Cruz, Seville, Spain
| | - Mª Ángeles Muñoz-Fernandez
- Molecular Immunology Laboratory, Hospital General Universitario Gregorio Marañón, Health Research Institute Gregorio Marañón (IiSGM), Madrid, Spain
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Maria Luisa Navarro-Gomez
- Grupo de Infecciones en la Población Pediátrica, Health Research Institute Gregorio Marañón (IiSGM), Calle Dr. Esquerdo 46, 28007, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBER-INFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Servicio de Pediatría, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Universidad Complutense de Madrid (UCM), Madrid, Spain
| | - Yolanda M Pacheco
- Immunology Service, Unit of Clinical Laboratories, Institute of Biomedicine of Seville, IBiS / Virgen del Rocío University Hospital / CSIC / University of Seville, Seville, Spain
- Facultad de Ciencias de La Salud, Universidad Loyola Andalucía, Campus Sevilla, Sevilla, Spain
| | - Manuel Leal
- Internal Medicine Service, Hospital Viamed Santa Ángela de la Cruz, Seville, Spain
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Hu J, Luo Z, Song J, Kong D, Li Z, Chen C, Sun S. High C-reactive protein is associated with the efficacy of neoadjuvant chemotherapy for hormone receptor-positive breast cancer. Medicine (Baltimore) 2024; 103:e40775. [PMID: 39612416 PMCID: PMC11608662 DOI: 10.1097/md.0000000000040775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Accepted: 11/13/2024] [Indexed: 12/01/2024] Open
Abstract
C-reactive protein (CRP) is a nonspecific biomarker for systemic inflammatory response and is linked to the prognosis of breast cancer (BC); however, few studies have investigated the correlation between CRP and the effectiveness of neoadjuvant chemotherapy treatment for BC. We recruited 177 patients with BC who underwent neoadjuvant chemotherapy in our clinical trial. the median CRP level (0.24 mg/L), patients were categorized into high and low groups. We examined the relationship between CRP levels and various clinicopathological factors, including pathological complete response (pCR), using the chi-square test or Fisher exact test. Furthermore, we evaluated the predictive capacity of CRP for different molecular subtypes by constructing receiver operating characteristic curves. To identify the independent variables associated with pCR, we conducted logistic regression multivariate analysis. No association was found between C-reactive levels at baseline and pCR rates. CRP level was significantly associated with higher body mass index, and the high CRP group had more overweight patients (47.06% vs. 16.30%, P < .001). In hormone receptor-positive patients, the high CRP group demonstrated a significantly higher pCR rate (OR = 4.115, 95% CI: 1.481-11.36, P = .009). The areas under the curve was 0.670 (95% CI: 0.550-0.792, P < .001). Multivariate logistic analysis showed that the CRP level was a significant independent predictor of pCR (OR = 5.882, 95% CI: 1.470-28.57, P = .017). High CRP levels were found to be associated with a higher pCR rate, indicating their independent predictive value in determining the efficacy of neoadjuvant chemotherapy in hormone receptor-positive BC patients.
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Affiliation(s)
- Jiawei Hu
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, PR China
| | - Zixuan Luo
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, PR China
| | - Junlong Song
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, PR China
| | - Deguang Kong
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, PR China
| | - Zhiyu Li
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, PR China
| | - Chuang Chen
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, PR China
| | - Shengrong Sun
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, PR China
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Turner L, Charrouf R, Martínez-Vizcaíno V, Hutchison A, Heilbronn LK, Fernández-Rodríguez R. The effects of time-restricted eating versus habitual diet on inflammatory cytokines and adipokines in the general adult population: a systematic review with meta-analysis. Am J Clin Nutr 2024; 119:206-220. [PMID: 37865184 DOI: 10.1016/j.ajcnut.2023.10.009] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 08/12/2023] [Accepted: 10/16/2023] [Indexed: 10/23/2023] Open
Abstract
BACKGROUND Time-restricted eating (TRE) may facilitate weight loss, but its impact on inflammation remains unclear. Chronic inflammation can detrimentally increase risk of obesity-associated comorbidities. OBJECTIVES The aim of this systematic review was to synthesize and determine the effects of TRE on cytokine and adipokines (C-reactive protein [CRP], TNF alpha [TNF-α], interleukin-6 [IL-6], leptin, and adiponectin) in adults. METHODS PubMed, Scopus, Cochrane CENTRAL, and Web of Science were systematically searched for randomized controlled trials (RCTs) and non-RCTs to determine the effects of TRE on cytokines and adipokines in adults up to 23 June, 2023. Risk of bias was assessed using risk of Bias 2 tool for RCTs and the ROBINS-I for non-RCTs. The standardized mean differences (SMDs) and their 95% confidence intervals (CIs) were estimated with the DerSimonian-Laird method through random-effect models. The PRISMA recommendations were followed. RESULTS A total of 25 studies (13 RCTs, 12 non-RCTs) involving 936 participants were included. The pooled SMD for the effect of TRE compared with the control group on cytokines and adipokines was -0.11 (95% CI: -0.33, 0.12; I2 = 19.7%; n = 10 comparisons) for CRP; -0.25 (95% CI: -0.47, -0.03; I2 = 0%; n = 11 comparisons) for TNF-α; -0.09 (95% CI: -0.39, 0.21; I2 = 16.4%; n = 8 comparisons) for IL-6; -0.81 (95% CI: -1.37, -0.24; I2 = 65.3%; n = 5 comparisons) for leptin; and 0.07 (95% CI: -0.40, 0.54; I2 = 56.9%; n = 6 comparisons) for adiponectin. CONCLUSIONS Time-restricted eating may be an effective approach to reduce TNF-α and leptin levels in the general adult population. This review was registered at PROSPERO as CRD42022358162.
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Affiliation(s)
- Laurent Turner
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia; South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia
| | - Rasha Charrouf
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia; South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia
| | - Vicente Martínez-Vizcaíno
- Universidad de Castilla La-Mancha, Health and Social Research Centre, Cuenca, Spain; Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Talca, Chile
| | - Amy Hutchison
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia; South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia
| | - Leonie K Heilbronn
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia; South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia.
| | - Rubén Fernández-Rodríguez
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia; South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia; Universidad de Castilla La-Mancha, Health and Social Research Centre, Cuenca, Spain
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Liu G, Bao L, Chen C, Xu J, Cui X. The implication of mesenteric functions and the biological effects of nanomaterials on the mesentery. NANOSCALE 2023; 15:12868-12879. [PMID: 37492026 DOI: 10.1039/d3nr02494f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/27/2023]
Abstract
A growing number of nanomaterials are being broadly used in food-related fields as well as therapeutics. Oral exposure to these widespread nanomaterials is inevitable, with the intestine being a major target organ. Upon encountering the intestine, these nanoparticles can cross the intestinal barrier, either bypassing cells or via endocytosis pathways to enter the adjacent mesentery. The intricate structure of the mesentery and its entanglement with the abdominal digestive organs determine the final fate of nanomaterials in the human body. Importantly, mesentery-governed dynamic processes determine the distribution and subsequent biological effects of nanomaterials that cross the intestine, thus there is a need to understand how nanomaterials interact with the mesentery. This review presents the recent progress in understanding the mesenteric structure and function and highlights the importance of the mesentery in health and disease, with a focus on providing new insights and research directions around the biological effects of nanomaterials on the mesentery. A thorough comprehension of the interactions between nanomaterials and the mesentery will facilitate the design of safer nanomaterial-containing products and the development of more effective nanomedicines to combat intestinal disorders.
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Affiliation(s)
- Guanyu Liu
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Lin Bao
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Chunying Chen
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.
- University of Chinese Academy of Sciences, Beijing 100049, China
- The GBA National Institute for Nanotechnology Innovation, Guangzhou 510700, Guangdong, China
| | - Jianfu Xu
- State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China.
| | - Xuejing Cui
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.
- University of Chinese Academy of Sciences, Beijing 100049, China
- The GBA National Institute for Nanotechnology Innovation, Guangzhou 510700, Guangdong, China
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Vales-Villamarín C, de Dios O, Pérez-Nadador I, Gavela-Pérez T, Soriano-Guillén L, Garcés C. Leptin Concentrations Determine the Association between High-Sensitivity C-Reactive Protein Levels and Body Mass Index in Prepubertal Children. Nutrients 2023; 15:nu15102388. [PMID: 37242271 DOI: 10.3390/nu15102388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 05/08/2023] [Accepted: 05/18/2023] [Indexed: 05/28/2023] Open
Abstract
Obesity is associated with the presence of low-grade inflammation even during childhood. The dysregulation in the secretion of adipokines, such as leptin, which occurs in obesity states, could be associated with an increase in inflammatory factors already at an early age. In this cross-sectional study, we aimed to investigate the role of leptin levels in the association between body mass index (BMI) and high-sensitivity C-reactive protein (hs-CRP) in healthy schoolchildren. Leptin and hs-CRP levels were analyzed in two pediatric cohorts comprising 684 prepubertal children and 763 adolescents. hs-CRP concentrations correlated significantly with BMI and leptin levels in prepubertal males and females as well as in adolescents. However, after adjusting for leptin concentration, no significant correlation was observed between hs-CRP and BMI in prepubertal children, while the correlations remained significant in adolescents. The same differences were observed when analyzed BMI according to hs-CRP tertile after adjusting for leptin; mean BMI was not significantly different between hs-CRP tertile in prepubertal children but was significantly different in adolescents. In conclusion, the fact that leptin concentrations determine the association of BMI with hs-CRP levels in prepubertal children, but not in adolescents, suggests a role for leptin in low-grade inflammation at early ages, while other factors seem to contribute to hs-CRP levels later in life.
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Affiliation(s)
| | - Olaya de Dios
- Lipid Research Laboratory, IIS-Fundación Jimenez Diaz, UAM, 28040 Madrid, Spain
| | - Iris Pérez-Nadador
- Lipid Research Laboratory, IIS-Fundación Jimenez Diaz, UAM, 28040 Madrid, Spain
| | - Teresa Gavela-Pérez
- Department of Pediatrics, IIS-Fundación Jimenez Diaz, UAM, 28040 Madrid, Spain
| | | | - Carmen Garcés
- Lipid Research Laboratory, IIS-Fundación Jimenez Diaz, UAM, 28040 Madrid, Spain
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Hojeij B, Rousian M, Sinclair KD, Dinnyes A, Steegers-Theunissen RPM, Schoenmakers S. Periconceptional biomarkers for maternal obesity: a systematic review. Rev Endocr Metab Disord 2023; 24:139-175. [PMID: 36520252 PMCID: PMC10023635 DOI: 10.1007/s11154-022-09762-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/01/2022] [Indexed: 12/23/2022]
Abstract
Periconceptional maternal obesity is linked to adverse maternal and neonatal outcomes. Identifying periconceptional biomarkers of pathways affected by maternal obesity can unravel pathophysiologic mechanisms and identify individuals at risk of adverse clinical outcomes. The literature was systematically reviewed to identify periconceptional biomarkers of the endocrine, inflammatory and one-carbon metabolic pathways influenced by maternal obesity. A search was conducted in Embase, Ovid Medline All, Web of Science Core Collection and Cochrane Central Register of Controlled Trials databases, complemented by manual search in PubMed until December 31st, 2020. Eligible studies were those that measured biomarker(s) in relation to maternal obesity, overweight/obesity or body mass index (BMI) during the periconceptional period (14 weeks preconception until 14 weeks post conception). The ErasmusAGE score was used to assess the quality of included studies. Fifty-one articles were included that evaluated over 40 biomarkers. Endocrine biomarkers associated with maternal obesity included leptin, insulin, thyroid stimulating hormone, adiponectin, progesterone, free T4 and human chorionic gonadotropin. C-reactive protein was associated with obesity as part of the inflammatory pathway, while the associated one-carbon metabolism biomarkers were folate and vitamin B12. BMI was positively associated with leptin, C-reactive protein and insulin resistance, and negatively associated with Free T4, progesterone and human chorionic gonadotropin. Concerning the remaining studied biomarkers, strong conclusions could not be established due to limited or contradictory data. Future research should focus on determining the predictive value of the optimal set of biomarkers for their use in clinical settings. The most promising biomarkers include leptin, adiponectin, human chorionic gonadotropin, insulin, progesterone and CRP.
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Affiliation(s)
- Batoul Hojeij
- Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, 3015GD, The Netherlands
| | - Melek Rousian
- Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, 3015GD, The Netherlands
| | - Kevin D Sinclair
- School of Biosciences, Sutton Bonnington Campus, University of Nottingham, Leicestershire, LE12 6HD, UK
| | - Andras Dinnyes
- BioTalentum Ltd., Godollo, 2100, Hungary
- Department of Cell Biology and Molecular Medicine, University of Szeged, Szeged, 6720, Hungary
- Department of Physiology and Animal Health, Institute of Physiology and Animal Nutrition, Hungarian University of Agriculture and Life Sciences, Godollo, 2100, Hungary
| | | | - Sam Schoenmakers
- Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, 3015GD, The Netherlands.
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Hinojosa-Moscoso A, Motger-Albertí A, De la Calle-Vargas E, Martí-Navas M, Biarnés C, Arnoriaga-Rodríguez M, Blasco G, Puig J, Luque-Córdoba D, Priego-Capote F, Moreno-Navarrete JM, Fernández-Real JM. The Longitudinal Changes in Subcutaneous Abdominal Tissue and Visceral Adipose Tissue Volumetries Are Associated with Iron Status. Int J Mol Sci 2023; 24:4750. [PMID: 36902180 PMCID: PMC10002479 DOI: 10.3390/ijms24054750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 02/20/2023] [Accepted: 02/26/2023] [Indexed: 03/06/2023] Open
Abstract
Excess iron is known to trigger adipose tissue dysfunction and insulin resistance. Circulating markers of iron status have been associated with obesity and adipose tissue in cross-sectional studies. We aimed to evaluate whether iron status is linked to changes in abdominal adipose tissue longitudinally. Subcutaneous abdominal tissue (SAT) and visceral adipose tissue (VAT) and its quotient (pSAT) were assessed using magnetic resonance imaging (MRI), at baseline and after one year of follow-up, in 131 (79 in follow-up) apparently healthy subjects, with and without obesity. Insulin sensitivity (euglycemic- hyperinsulinemic clamp) and markers of iron status were also evaluated. Baseline serum hepcidin (p = 0.005 and p = 0.002) and ferritin (p = 0.02 and p = 0.01)) were associated with an increase in VAT and SAT over one year in all subjects, while serum transferrin (p = 0.01 and p = 0.03) and total iron-binding capacity (p = 0.02 and p = 0.04) were negatively associated. These associations were mainly observed in women and in subjects without obesity, and were independent of insulin sensitivity. After controlling for age and sex, serum hepcidin was significantly associated with changes in subcutaneous abdominal tissue index (iSAT) (β = 0.406, p = 0.007) and visceral adipose tissue index (iVAT) (β = 0.306, p = 0.04), while changes in insulin sensitivity (β = 0.287, p = 0.03) and fasting triglycerides (β = -0.285, p = 0.03) were associated with changes in pSAT. These data indicated that serum hepcidin are associated with longitudinal changes in SAT and VAT, independently of insulin sensitivity. This would be the first prospective study evaluating the redistribution of fat according to iron status and chronic inflammation.
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Affiliation(s)
- Alejandro Hinojosa-Moscoso
- Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IdibGi), 17007 Girona, Spain
- Department of Medical Sciences, School of Medicine, University of Girona, 17003 Girona, Spain
| | - Anna Motger-Albertí
- Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IdibGi), 17007 Girona, Spain
- Department of Medical Sciences, School of Medicine, University of Girona, 17003 Girona, Spain
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIEROBN), 28029 Madrid, Spain
| | - Elena De la Calle-Vargas
- Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IdibGi), 17007 Girona, Spain
- Department of Medical Sciences, School of Medicine, University of Girona, 17003 Girona, Spain
| | - Marian Martí-Navas
- Medical Imaging, Girona Biomedical Research Institute (IdibGi), 17007 Girona, Spain
| | - Carles Biarnés
- Medical Imaging, Girona Biomedical Research Institute (IdibGi), 17007 Girona, Spain
| | - María Arnoriaga-Rodríguez
- Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IdibGi), 17007 Girona, Spain
- Department of Medical Sciences, School of Medicine, University of Girona, 17003 Girona, Spain
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIEROBN), 28029 Madrid, Spain
| | - Gerard Blasco
- Medical Imaging, Girona Biomedical Research Institute (IdibGi), 17007 Girona, Spain
- Department of Radiology (IDI), Dr. Josep Trueta University Hospital, 17007 Girona, Spain
| | - Josep Puig
- Department of Medical Sciences, School of Medicine, University of Girona, 17003 Girona, Spain
- Medical Imaging, Girona Biomedical Research Institute (IdibGi), 17007 Girona, Spain
- Department of Radiology (IDI), Dr. Josep Trueta University Hospital, 17007 Girona, Spain
| | - Diego Luque-Córdoba
- Department of Analytical Chemistry, University of Córdoba, Annex Marie Curie Building, Campus of Rabanales, 14014 Córdoba, Spain
- Consortium for Biomedical Research in Frailty & Healthy Ageing (CIBERFES), Carlos III Institute of Health, 28029 Madrid, Spain
| | - Feliciano Priego-Capote
- Department of Analytical Chemistry, University of Córdoba, Annex Marie Curie Building, Campus of Rabanales, 14014 Córdoba, Spain
- Consortium for Biomedical Research in Frailty & Healthy Ageing (CIBERFES), Carlos III Institute of Health, 28029 Madrid, Spain
| | - José María Moreno-Navarrete
- Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IdibGi), 17007 Girona, Spain
- Department of Medical Sciences, School of Medicine, University of Girona, 17003 Girona, Spain
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIEROBN), 28029 Madrid, Spain
| | - José Manuel Fernández-Real
- Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IdibGi), 17007 Girona, Spain
- Department of Medical Sciences, School of Medicine, University of Girona, 17003 Girona, Spain
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIEROBN), 28029 Madrid, Spain
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9
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Lee C, Min SH, Niitsu K. C-Reactive Protein and Specific Depression Symptoms Among Older Adults: An Exploratory Investigation of Multi-Plane Networks Using Cross-Sectional Data From NHANES (2017-2020). Biol Res Nurs 2023; 25:14-23. [PMID: 35732288 DOI: 10.1177/10998004221110602] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Studies investigating the association between C-reactive protein (CRP) and depression among older adults have yielded inconsistent results. We suspect that this may be due to varying associations between CRP and particular depression symptom criteria, and we addressed this challenge using network analysis. METHODS We used cross-sectional data from prepandemic National Health and Nutrition Examination Survey questionnaires (2017-2020) and included a sample of 1698 adults aged 65 years or older. Depression symptoms were assessed using the Patient Health Questionnaire-9. Unregularized Mixed Graphical Models were estimated using the R package mgm before and after adjusting for relevant sociodemographic, clinical, and lifestyle covariates. RESULTS In the model with no covariates, the only symptom criterion associated with CRP was "appetite problems." This association remained robust after controlling for all covariates. Although not associated with CRP, other criteria such as "fatigue" and "concentration difficulty" showed associations with important covariates for older adults such as white blood cell count or hemoglobin, respectively. DISCUSSION The CRP-related variability in the depression symptom network that we have demonstrated may help explain the reported inconsistencies. The present study stands as exploratory, and future research should focus on applying longitudinal designs and including several other inflammatory proteins and covariates that were not measured in the current network model.
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Affiliation(s)
- Chiyoung Lee
- School of Nursing and Health Studies, 52576University of Washington Bothell, Bothell, WA, USA
| | - Se Hee Min
- 15776Duke University School of Nursing, Durham, NC, USA
| | - Kosuke Niitsu
- School of Nursing and Health Studies, 52576University of Washington Bothell, Bothell, WA, USA
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10
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Lino RDS, Silva MSDP, de Jesus DS, de Macedo RC, Lagares LS, dos Santos FNA, de Almeida LAB, Bomfim ES, dos Santos CPC. Molecular aspects of COVID-19 and its relationship with obesity and physical activity: a narrative review. SAO PAULO MED J 2023; 141:78-86. [PMID: 36102458 PMCID: PMC9808989 DOI: 10.1590/1516-3180.2021.1038.r1.06072022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 07/06/2022] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Severe acute respiratory syndrome coronavirus 2 has several mechanisms of action related to inflammatory responses, especially in individuals diagnosed with obesity. This hyperinflammatory clinical profile resulting from the association between obesity and coronavirus disease 2019 (COVID-19) may be attenuated by regular physical activity. OBJECTIVE The aim of this study was to review the evidence on the consequences of physical inactivity and physical activity on COVID-19 in patients with obesity. DESIGN AND SETTING Narrative review at the Bahiana School of Medicine and Public Health in Salvador, Brazil. METHODS We searched evidence on the association of COVID-19 with physical activity and obesity using the following keywords: "covid-19," "physical activity," and "obesity". The databases used were MEDLINE (PubMed), ScienceDirect, and Virtual Health Library. Studies published from 2019 to 2021 and available in Portuguese, English, and Spanish were included. The final search was conducted on September 26, 2021. RESULTS We identified 661 studies in the database, among which 71 were considered for inclusion in the narrative review of the molecular aspects of COVID-19 and its relationship with physical activity and obesity. CONCLUSION This literature review enabled the perception of the relationship between the molecular mechanisms of COVID-19 and obesity. Regular physical activity had various benefits for the inflammatory condition of the studied population, highlighting moderate-intensity.
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Affiliation(s)
- Ramon de Souza Lino
- BSc. Physical Education Professional, Research Group on Metabolic Diseases, Physical Exercise and Health Technologies, Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador (BA), Brazil
| | - Mariana Sousa de Pina Silva
- Undergraduate Student, Research Group on Metabolic Diseases, Physical Exercise, and Health Technologies, Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador (BA), Brazil
| | - Daniel Simões de Jesus
- PhD. Assistant Professor, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Rodrigo Colares de Macedo
- Undergraduate Student, Research Group on Metabolic Diseases, Physical Exercise and Health Technologies, Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador (BA), Brazil
| | - Laura Souza Lagares
- BSc. Physical Education Professional, Research Group on Metabolic Diseases, Physical Exercise and Health Technologies, Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador (BA), Brazil
| | - Felipe Nunes Almeida dos Santos
- BSc. Physical Education Professional, Research Group on Metabolic Diseases, Physical Exercise and Health Technologies, Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador (BA), Brazil
| | - Luiz Alberto Bastos de Almeida
- MSc. Assistant Professor, Laboratory of Physical Activity, Universidade Estadual de Feira de Santana (UEFS), Feira de Santana (BA), Brazil
| | - Eric Simas Bomfim
- BSc. Physical Education Professional, Research Group on Metabolic Diseases, Physical Exercise and Health Technologies, Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador (BA), Brazil
| | - Clarcson Plácido Conceição dos Santos
- PhD. Assistant Professor, Research Group on Metabolic Diseases, Physical Exercise and Health Technologies, Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador (BA), Brazil
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11
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Costa A, de Brito GAP. Aerobic Exercise Associated with Fish Oil Supplementation Decreases C-Reactive Protein and Interleukin-6 in Celiac Disease Patients. J Nutr Metab 2022; 2022:3908675. [PMID: 35910449 PMCID: PMC9334128 DOI: 10.1155/2022/3908675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 07/05/2022] [Indexed: 12/02/2022] Open
Abstract
Background Several studies indicate that celiac disease patients present alterations within anthropometric, metabolic, and inflammatory parameters, while physical exercise and fish oil are known to activate modulatory pathways of such parameters. Objective To investigate the effects of a 12-week-long protocol of aerobic exercise and its association with fish oil supplementation in nineteen adult celiac disease patients. Material and Methods. The celiacs were divided into 2 groups: (A) FOS: supplementation (n = 11); and (B) EXE: supplementation and exercise (n = 8). The celiac groups were compared to the adult healthy control group (CTR) (n 12). Aerobic exercises were performed weekly, in three sessions of 60 minutes each, with a maximal heart rate intensity of 60-70%. The participants received 2 g/day of fish oil, a daily intake of 420 mg of eicosapentaenoic acid, and 230 mg of docosahexaenoic acid. The following measurements were taken in four phases: (A) anthropometry: body mass, height, body mass index, waist-to-hip ratio, fat mass, and fat-free mass; (B) metabolic profile: total cholesterol, triglycerides, HDL, and LDL; and (C) inflammatory profile: C-reactive protein and interleukin-6. Results Supplementation associated with aerobic exercise promoted a significant reduction in C-reactive protein (P < 0.01) and increased the proportion of individuals in the undetectable range of interleukin-6. Conclusions The associated interventions showed a corrective and preventive potential in relation to disorders associated with chronic inflammation; however, the experimental design does not allow us to discriminate between the biological effects that are dependent on the association between interventions and those exclusively dependent on aerobic exercise.
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Affiliation(s)
- Allysson Costa
- Laboratory of Physiology and Developmental Biology, Federal University of Latin American Integration—UNILA, Foz do Iguaçu, Paraná, Brazil
| | - Gleisson A. P. de Brito
- Laboratory of Physiology and Developmental Biology, Federal University of Latin American Integration—UNILA, Foz do Iguaçu, Paraná, Brazil
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12
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Laurain A, Rubera I, Razzouk-Cadet M, Bonnafous S, Albuquerque M, Paradis V, Patouraux S, Duranton C, Lesaux O, Lefthériotis G, Tran A, Anty R, Gual P, Iannelli A, Favre G. Arterial Calcifications in Patients with Liver Cirrhosis Are Linked to Hepatic Deficiency of Pyrophosphate Production Restored by Liver Transplantation. Biomedicines 2022; 10:1496. [PMID: 35884801 PMCID: PMC9312703 DOI: 10.3390/biomedicines10071496] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 06/11/2022] [Accepted: 06/14/2022] [Indexed: 11/24/2022] Open
Abstract
Liver fibrosis is associated with arterial calcification (AC). Since the liver is a source of inorganic pyrophosphate (PPi), an anti-calcifying compound, we investigated the relationship between plasma PPi ([PPi]pl), liver fibrosis, liver function, AC, and the hepatic expression of genes regulating PPi homeostasis. To that aim, we compared [PPi]pl before liver transplantation (LT) and 3 months after LT. We also assessed the expression of four key regulators of PPi in liver tissues and established correlations between AC, and scores of liver fibrosis and liver failure in these patients. LT candidates with various liver diseases were included. AC scores were assessed in coronary arteries, abdominal aorta, and aortic valves. Liver fibrosis was evaluated on liver biopsies and from non-invasive tests (FIB-4 and APRI scores). Liver functions were assessed by measuring serum albumin, ALBI, MELD, and Pugh−Child scores. An enzymatic assay was used to dose [PPi]pl. A group of patients without liver alterations from a previous cohort provided a control group. Gene expression assays were performed with mRNA extracted from liver biopsies and compared between LT recipients and the control individuals. [PPi]pl negatively correlated with APRI (r = −0.57, p = 0.001, n = 29) and FIB-4 (r = −0.47, p = 0.006, n = 29) but not with interstitial fibrosis index from liver biopsies (r = 0.07, p = 0.40, n = 16). Serum albumin positively correlated with [PPi]pl (r = 0.71; p < 0.0001, n = 20). ALBI, MELD, and Pugh−Child scores correlated negatively with [PPi]pl (r = −0.60, p = 0.0005; r = −0.56, p = 0.002; r = −0.41, p = 0.02, respectively, with n = 20). Liver fibrosis assessed on liver biopsies by FIB-4 and by APRI positively correlated with coronary AC (r = 0.51, p = 0.02, n = 16; r = 0.58, p = 0.009, n = 20; r = 0.41, p = 0.04, n = 20, respectively) and with abdominal aorta AC (r = 0.50, p = 0.02, n = 16; r = 0.67, p = 0.002, n = 20; r = 0.61, p = 0.04, n = 20, respectively). FIB-4 also positively correlated with aortic valve calcification (r = 0.40, p = 0.046, n = 20). The key regulator genes of PPi production in liver were lower in patients undergoing liver transplantation as compared to controls. Three months after surgery, serum albumin levels were restored to physiological levels (40 [37−44] vs. 35 [30−40], p = 0.009) and [PPi]pl was normalized (1.40 [1.07−1.86] vs. 0.68 [0.53−0.80] µmol/L, p = 0.0005, n = 12). Liver failure and/or fibrosis correlated with AC in several arterial beds and were associated with low plasma PPi and dysregulation of key proteins involved in PPi homeostasis. Liver transplantation normalized these parameters.
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Affiliation(s)
- Audrey Laurain
- Department of Nephrology, Pasteur 1 University Hospital, 06001 Nice, France;
- Faculty of Medicine, Tour Pasteur, 28 Avenue de Valombrose, University of Côte d’Azur, 06000 Nice, France; (I.R.); (S.B.); (S.P.); (C.D.); (G.L.); (A.T.); (R.A.); (P.G.); (A.I.)
- LP2M CNRS UMR 7370, Tour Pasteur, 28 Avenue de Valombrose, 06000 Nice, France
| | - Isabelle Rubera
- Faculty of Medicine, Tour Pasteur, 28 Avenue de Valombrose, University of Côte d’Azur, 06000 Nice, France; (I.R.); (S.B.); (S.P.); (C.D.); (G.L.); (A.T.); (R.A.); (P.G.); (A.I.)
- LP2M CNRS UMR 7370, Tour Pasteur, 28 Avenue de Valombrose, 06000 Nice, France
| | | | - Stéphanie Bonnafous
- Faculty of Medicine, Tour Pasteur, 28 Avenue de Valombrose, University of Côte d’Azur, 06000 Nice, France; (I.R.); (S.B.); (S.P.); (C.D.); (G.L.); (A.T.); (R.A.); (P.G.); (A.I.)
- Team 8 “Chronic Liver Diseases Associated with Obesity and Alcohol” Inserm, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M) Bâtiment Universitaire ARCHIMED? 151 Route Saint Antoine de Ginestière BP 2 3194, 06204 Nice, France
- Digestive Unit, Archet 2 University Hospital, 06200 Nice, France
| | - Miguel Albuquerque
- Pathology Department, Beaujon University Hospital, AP-HP, 92110 Clichy, France; (M.A.); (V.P.)
- Inserm U1149, Beaujon University Hospital, 92110 Clichy, France
| | - Valérie Paradis
- Pathology Department, Beaujon University Hospital, AP-HP, 92110 Clichy, France; (M.A.); (V.P.)
- Inserm U1149, Beaujon University Hospital, 92110 Clichy, France
| | - Stéphanie Patouraux
- Faculty of Medicine, Tour Pasteur, 28 Avenue de Valombrose, University of Côte d’Azur, 06000 Nice, France; (I.R.); (S.B.); (S.P.); (C.D.); (G.L.); (A.T.); (R.A.); (P.G.); (A.I.)
- Pathology Department, Pasteur 1 University Hospital, 06000 Nice, France
| | - Christophe Duranton
- Faculty of Medicine, Tour Pasteur, 28 Avenue de Valombrose, University of Côte d’Azur, 06000 Nice, France; (I.R.); (S.B.); (S.P.); (C.D.); (G.L.); (A.T.); (R.A.); (P.G.); (A.I.)
- LP2M CNRS UMR 7370, Tour Pasteur, 28 Avenue de Valombrose, 06000 Nice, France
| | - Olivier Lesaux
- Department Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813-5534, USA;
| | - Georges Lefthériotis
- Faculty of Medicine, Tour Pasteur, 28 Avenue de Valombrose, University of Côte d’Azur, 06000 Nice, France; (I.R.); (S.B.); (S.P.); (C.D.); (G.L.); (A.T.); (R.A.); (P.G.); (A.I.)
- LP2M CNRS UMR 7370, Tour Pasteur, 28 Avenue de Valombrose, 06000 Nice, France
- Department of Vascular Medicine and Surgery, Pasteur 1 University Hospital, 06000 Nice, France
| | - Albert Tran
- Faculty of Medicine, Tour Pasteur, 28 Avenue de Valombrose, University of Côte d’Azur, 06000 Nice, France; (I.R.); (S.B.); (S.P.); (C.D.); (G.L.); (A.T.); (R.A.); (P.G.); (A.I.)
- Team 8 “Chronic Liver Diseases Associated with Obesity and Alcohol” Inserm, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M) Bâtiment Universitaire ARCHIMED? 151 Route Saint Antoine de Ginestière BP 2 3194, 06204 Nice, France
- Digestive Unit, Archet 2 University Hospital, 06200 Nice, France
| | - Rodolphe Anty
- Faculty of Medicine, Tour Pasteur, 28 Avenue de Valombrose, University of Côte d’Azur, 06000 Nice, France; (I.R.); (S.B.); (S.P.); (C.D.); (G.L.); (A.T.); (R.A.); (P.G.); (A.I.)
- Team 8 “Chronic Liver Diseases Associated with Obesity and Alcohol” Inserm, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M) Bâtiment Universitaire ARCHIMED? 151 Route Saint Antoine de Ginestière BP 2 3194, 06204 Nice, France
- Digestive Unit, Archet 2 University Hospital, 06200 Nice, France
| | - Philippe Gual
- Faculty of Medicine, Tour Pasteur, 28 Avenue de Valombrose, University of Côte d’Azur, 06000 Nice, France; (I.R.); (S.B.); (S.P.); (C.D.); (G.L.); (A.T.); (R.A.); (P.G.); (A.I.)
- Team 8 “Chronic Liver Diseases Associated with Obesity and Alcohol” Inserm, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M) Bâtiment Universitaire ARCHIMED? 151 Route Saint Antoine de Ginestière BP 2 3194, 06204 Nice, France
| | - Antonio Iannelli
- Faculty of Medicine, Tour Pasteur, 28 Avenue de Valombrose, University of Côte d’Azur, 06000 Nice, France; (I.R.); (S.B.); (S.P.); (C.D.); (G.L.); (A.T.); (R.A.); (P.G.); (A.I.)
- Team 8 “Chronic Liver Diseases Associated with Obesity and Alcohol” Inserm, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M) Bâtiment Universitaire ARCHIMED? 151 Route Saint Antoine de Ginestière BP 2 3194, 06204 Nice, France
- Digestive Unit, Archet 2 University Hospital, 06200 Nice, France
| | - Guillaume Favre
- Department of Nephrology, Pasteur 1 University Hospital, 06001 Nice, France;
- Faculty of Medicine, Tour Pasteur, 28 Avenue de Valombrose, University of Côte d’Azur, 06000 Nice, France; (I.R.); (S.B.); (S.P.); (C.D.); (G.L.); (A.T.); (R.A.); (P.G.); (A.I.)
- LP2M CNRS UMR 7370, Tour Pasteur, 28 Avenue de Valombrose, 06000 Nice, France
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13
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Stanimirovic J, Radovanovic J, Banjac K, Obradovic M, Essack M, Zafirovic S, Gluvic Z, Gojobori T, Isenovic ER. Role of C-Reactive Protein in Diabetic Inflammation. Mediators Inflamm 2022; 2022:3706508. [PMID: 35620114 PMCID: PMC9129992 DOI: 10.1155/2022/3706508] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/20/2022] [Accepted: 04/29/2022] [Indexed: 01/08/2023] Open
Abstract
Even though type 2 diabetes mellitus (T2DM) represents a worldwide chronic health issue that affects about 462 million people, specific underlying determinants of insulin resistance (IR) and impaired insulin secretion are still unknown. There is growing evidence that chronic subclinical inflammation is a triggering factor in the origin of T2DM. Increased C-reactive protein (CRP) levels have been linked to excess body weight since adipocytes produce tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), which are pivotal factors for CRP stimulation. Furthermore, it is known that hepatocytes produce relatively low rates of CRP in physiological conditions compared to T2DM patients, in which elevated levels of inflammatory markers are reported, including CRP. CRP also participates in endothelial dysfunction, the production of vasodilators, and vascular remodeling, and increased CRP level is closely associated with vascular system pathology and metabolic syndrome. In addition, insulin-based therapies may alter CRP levels in T2DM. Therefore, determining and clarifying the underlying CRP mechanism of T2DM is imperative for novel preventive and diagnostic procedures. Overall, CRP is one of the possible targets for T2DM progression and understanding the connection between insulin and inflammation may be helpful in clinical treatment and prevention approaches.
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Affiliation(s)
- Julijana Stanimirovic
- Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Jelena Radovanovic
- Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Katarina Banjac
- Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Milan Obradovic
- Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Magbubah Essack
- King Abdullah University of Science and Technology (KAUST), Computer, Electrical, and Mathematical Sciences and Engineering (CEMSE) Division, Computational Bioscience Research Center (CBRC), Thuwal, Saudi Arabia
| | - Sonja Zafirovic
- Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Zoran Gluvic
- University Clinical-Hospital Centre Zemun-Belgrade, Clinic of Internal Medicine, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Takashi Gojobori
- King Abdullah University of Science and Technology (KAUST), Computer, Electrical, and Mathematical Sciences and Engineering (CEMSE) Division, Computational Bioscience Research Center (CBRC), Thuwal, Saudi Arabia
| | - Esma R. Isenovic
- Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
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14
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Zhao RR, Mavros Y, Meiklejohn J, Anderberg KA, Singh N, Kay S, Baker MK, Wang Y, Climstein M, O'Sullivan A, De Vos N, Baune BT, Blair SN, Simar D, Singh MAF. Effect of High Intensity Power Training on Cognitive Function in Older Adults with Type 2 Diabetes: Secondary Outcomes of the GREAT2DO Study. J Gerontol A Biol Sci Med Sci 2022; 77:1975-1985. [PMID: 35436329 PMCID: PMC9536451 DOI: 10.1093/gerona/glac090] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Indexed: 12/04/2022] Open
Abstract
We sought to determine the effects of 12 months of power training on cognition, and whether improvements in body composition, muscle strength, and/or aerobic capacity (VO2peak) were associated with improvements in cognition in older adults with type 2 diabetes (T2D). Participants with T2D were randomized to power training or low-intensity sham exercise control condition, 3 days per week for 12 months. Cognitive outcomes included memory, attention/speed, executive function, and global cognition. Other relevant outcomes included VO2peak, strength, and whole body and regional body composition. One hundred and three adults with T2D (mean age 67.9 years; standard deviation [SD] 5.9; 50.5% women) were enrolled and analyzed. Unexpectedly, there was a nearly significant improvement in global cognition (p = .05) in the sham group relative to power training, although both groups improved over time (p < .01). There were significant interactions between group allocation and body composition or muscle strength in the models predicting cognitive changes. Therefore, after stratifying by group allocation, improvements in immediate memory were associated with increases in relative skeletal muscle mass (r = 0.38, p = .03), reductions in relative body fat (r = −0.40, p = .02), and increases in knee extension strength were directly related to changes in executive function (r = −0.41, p = .02) within the power training group. None of these relationships were present in the sham group (p > .05). Although power training did not significantly improve cognition compared to low-intensity exercise control, improvements in cognitive function in older adults were associated with hypothesized improvements in body composition and strength after power training.
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Affiliation(s)
- Ren Ru Zhao
- Exercise Health and Performance Faculty Research Group, Faculty of Medicine and Health, University of Sydney, Camperdown, Australia.,University of Longyan, Fujian, China.,Clinical Rehabilitation Research Group, Longyan Renmin Hospital, China
| | - Yorgi Mavros
- Exercise Health and Performance Faculty Research Group, Faculty of Medicine and Health, University of Sydney, Camperdown, Australia
| | - Jacinda Meiklejohn
- Exercise Health and Performance Faculty Research Group, Faculty of Medicine and Health, University of Sydney, Camperdown, Australia
| | - Kylie A Anderberg
- Exercise Health and Performance Faculty Research Group, Faculty of Medicine and Health, University of Sydney, Camperdown, Australia
| | - Nalin Singh
- Exercise Health and Performance Faculty Research Group, Faculty of Medicine and Health, University of Sydney, Camperdown, Australia
| | - Shelley Kay
- Centre for Medical Psychology and Evidence Based Decision Making, Faculty of Medicine, University of Sydney, Camperdown, Australia
| | - Michael K Baker
- Research Ethics and Integrity, Australian Catholic University, Strathfield, Australia.,Clinical Exercise Physiology, School of Behavioural and Health Sciences, Australian Catholic University, Strathfield, Australia
| | - Yi Wang
- Lipid Metabolism & Cardiometabolic Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
| | - Mike Climstein
- School of Health and Human Sciences, Southern Cross University, Gold Coast, Australia
| | - Anthony O'Sullivan
- Department of Endocrinology, Faculty of Medicine, University of New South Wales, Sydney, Australia
| | - Nathan De Vos
- The Centre for STRONG Medicine, Balmain Hospital, Australia
| | - Bernhard T Baune
- Department of Psychiatry, University of Münster, Münster, Germany.,Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Australia.,The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Australia
| | - Steven N Blair
- Exercise Science Arnold School of Public Health, University of South Carolina, Columbia, USA
| | - David Simar
- School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia
| | - Maria A Fiatarone Singh
- Exercise Health and Performance Faculty Research Group, Faculty of Medicine and Health, University of Sydney, Camperdown, Australia.,Sydney Medical School, University of Sydney, Camperdown, Australia.,Jean Mayer USDA Human Nutrition Research Centre on Aging, Tufts University, Boston, USA
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15
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Suau R, Pardina E, Domènech E, Lorén V, Manyé J. The Complex Relationship Between Microbiota, Immune Response and Creeping Fat in Crohn's Disease. J Crohns Colitis 2022; 16:472-489. [PMID: 34528668 DOI: 10.1093/ecco-jcc/jjab159] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
In the last decade, there has been growing interest in the pathological involvement of hypertrophic mesenteric fat attached to the serosa of the inflamed intestinal segments involved in Crohn's disease [CD], known as creeping fat. In spite of its protective nature, creeping fat harbours an aberrant inflammatory activity which, in an already inflamed intestine, may explain why creeping fat is associated with a greater severity of CD. The transmural inflammation of CD facilitates the interaction of mesenteric fat with translocated intestinal microorganisms, contributing to activation of the immune response. This may be not the only way in which microorganisms alter the homeostasis of this fatty tissue: intestinal dysbiosis may also impair xenobiotic metabolism. All these CD-related alterations have a functional impact on nuclear receptors such as the farnesoid X receptor or the peroxisome proliferator-activated receptor γ, which are implicated in regulation of the immune response, adipogenesis and the maintenance of barrier function, as well as on creeping fat production of inflammatory-associated cells such as adipokines. The dysfunction of creeping fat worsens the inflammatory course of CD and may favour intestinal fibrosis and fistulizing complications. However, our current knowledge of the pathophysiology and pathogenic role of creeping fat is controversial and a better understanding might provide new therapeutic targets for CD. Here we aim to review and update the key cellular and molecular alterations involved in this inflammatory process that link the pathological components of CD with the development of creeping fat.
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Affiliation(s)
- Roger Suau
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain
| | - Eva Pardina
- Biochemistry and Molecular Biomedicine Department, University of Barcelona, Barcelona (Catalonia), Spain
| | - Eugeni Domènech
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain.,Gastroenterology Department, 'Germans Trias i Pujol' University Hospital, Badalona (Catalonia), Spain
| | - Violeta Lorén
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain
| | - Josep Manyé
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain
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16
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Zhang X, Wang M, Hao Y, Xu B, Tian L, Miao Y, Cheng L, Li J. Association of C-reactive protein with breast cancer is stronger for the potentially obese women: A Chinese case-control study and meta-analysis of 19 studies. J Evid Based Med 2021; 14:275-277. [PMID: 34644009 DOI: 10.1111/jebm.12455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 06/06/2021] [Accepted: 09/13/2021] [Indexed: 12/09/2022]
Affiliation(s)
- Xiaofan Zhang
- Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
- Office of Academic Research, The Affiliated Jinyang Hospital of Guizhou Medical University, Guiyang, China
| | - Mengyuan Wang
- Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Yu Hao
- Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Bin Xu
- Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Lulu Tian
- Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Yunqi Miao
- Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Long Cheng
- Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Jiayuan Li
- Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
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17
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Pan F, Tian J, Cicuttini F, Jones G. Prospective Association Between Inflammatory Markers and Knee Cartilage Volume Loss and Pain Trajectory. Pain Ther 2021; 11:107-119. [PMID: 34837639 PMCID: PMC8861228 DOI: 10.1007/s40122-021-00341-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 11/10/2021] [Indexed: 01/15/2023] Open
Abstract
Introduction Inflammation has been suggested to be involved in the pathogenesis of osteoarthritis and pain. We sought to explore the associations between inflammatory serum markers and magnetic resonance imaging-defined long-term structural change and pain trajectory. Methods A total of 169 randomly selected participants (mean age 63 years; 47% female) from a prospective cohort study were included in this study. Circulating levels of interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-α) and high-sensitivity C-reactive protein (CRP) were measured at baseline. A knee MRI scan was performed to measure cartilage volume (CV) and bone marrow lesions (BMLs) at baseline and at 10.7 years. Knee pain at four visits was measured by the WOMAC pain questionnaire, and pain trajectories were identified using group-based trajectory modelling. Linear, log-binomial and multi-nominal logistic regression were used for the analyses. Results IL-6 was associated with lateral but not medial tibial CV loss (β = − 0.25% per annum, per standard deviation [SD] log pg/ml; P < 0.05) in the multivariate analysis. IL-6 was also associated with a ‘Moderate pain’ trajectory (relative risk ratio 1.93 per SD log pg/ml; 95% confidence interval 1.02–3.65) relative to the ‘Minimal pain’ trajectory group. There was no significant association of TNF-α and CRP with CV loss and pain trajectory groups with the exception of a beneficial relationship between CRP and medial tibial CV loss (β = 0.20% per annum, per SD log mg/l). No association between inflammatory markers and change in BML size was observed. Conclusions IL-6 was independently associated with compartment-specific CV loss and worse pain trajectory, but the other markers studied were not, suggesting that components of inflammation are implicated in the pathogenesis of cartilage loss and developing a worse pain course. Supplementary Information The online version contains supplementary material available at 10.1007/s40122-021-00341-1.
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Affiliation(s)
- Feng Pan
- Menzies Institute for Medical Research, University of Tasmania, Private Bag 23, Hobart, TAS, 7000, Australia.
| | - Jing Tian
- Menzies Institute for Medical Research, University of Tasmania, Private Bag 23, Hobart, TAS, 7000, Australia
| | - Flavia Cicuttini
- Department of Epidemiology and Preventive Medicine, Monash University Medical School, Commercial Road, Melbourne, VIC, 3181, Australia
| | - Graeme Jones
- Menzies Institute for Medical Research, University of Tasmania, Private Bag 23, Hobart, TAS, 7000, Australia
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18
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Abu-Shahba N, Mahmoud M, El-Erian AM, Husseiny MI, Nour-Eldeen G, Helwa I, Amr K, ElHefnawi M, Othman AI, Ibrahim SA, Azmy O. Impact of type 2 diabetes mellitus on the immunoregulatory characteristics of adipose tissue-derived mesenchymal stem cells. Int J Biochem Cell Biol 2021; 140:106072. [PMID: 34455058 DOI: 10.1016/j.biocel.2021.106072] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 08/02/2021] [Accepted: 08/24/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder associated with several complications. Adipose tissue-derived mesenchymal stem cells (AT-MSCs) represent an emerging type of MSCs with high plasticity and immunoregulatory capabilities and are useful for treating inflammation-related disorders such as T2DM. However, the pathogenic microenvironment of T2DM may affect their therapeutic potential. We aimed to examine the impact of the diabetic milieu on the immunomodulatory/anti-inflammatory potential of AT-MSCs. METHODS We assessed the proliferation potential, cell surface expression of MSC-characteristic markers and immunomodulatory markers, along with the gene expression and protein secretion of pro-inflammatory and anti-inflammatory cytokines and adipokines in AT-MSCs derived from T2DM patients (dAT-MSCs) vs. those derived from non-diabetic volunteers (ndAT-MSCs). Furthermore, we evaluated the IFN-γ priming effect on both groups. RESULTS Our data revealed comparable proliferative activities in both groups. Flow cytometric analysis results showed a lower expression of CD200 and CD276 on dAT-MSCs vs. ndAT-MSCs. qPCR demonstrated upregulation of IL-1β associated with a downregulation of IL-1RN in dAT-MSCs vs. ndAT-MSCs. IFN-γ priming induced an elevation in CD274 expression associated with IDO1 and ILRN overexpression and IL-1β downregulation in both groups. ELISA analysis uncovered elevated levels of secreted IL-1β, TNF, and visfatin/NAMPT in dAT-MSCs, whereas IL-1RA and IDO levels were reduced. ELISA results were also evident in the secretome of dAT-MSCs upon IFN-γ priming. CONCLUSIONS This study suggests that the T2DM milieu alters the immunomodulatory characteristics of AT-MSCs with a shift towards a proinflammatory phenotype which may restrain their autologous therapeutic use. Furthermore, our findings indicate that IFN-γ priming could be a useful strategy for enhancing dAT-MSC anti-inflammatory potential.
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Affiliation(s)
- Nourhan Abu-Shahba
- Stem Cell Research Group, Medical Research Centre of Excellence, National Research Centre, Cairo, Egypt; Department of Medical Molecular Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
| | - Marwa Mahmoud
- Stem Cell Research Group, Medical Research Centre of Excellence, National Research Centre, Cairo, Egypt; Department of Medical Molecular Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt
| | - Alaa Mohammed El-Erian
- Department of Endocrine Surgery, National Institute of Diabetes and Endocrinology, Cairo, Egypt
| | - Mohamed Ibrahim Husseiny
- Department of Translational Research and Cellular Therapeutics, Arthur Riggs DMRI, Beckman Research Institute, City of Hope, National Medical Center, Durate, CA, USA; Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
| | - Ghada Nour-Eldeen
- Stem Cell Research Group, Medical Research Centre of Excellence, National Research Centre, Cairo, Egypt; Department of Molecular Genetics and Enzymology, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt
| | - Iman Helwa
- Department of Immunogenetics, Human Genetics and Genome Research Division, National Resrearch Centre, Egypt
| | - Khalda Amr
- Department of Medical Molecular Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt
| | - Mahmoud ElHefnawi
- Biomedical Informatics and Chemoinformatics Group, Informatics and Systems Department, National Research Centre, Cairo, Egypt
| | - Amel Ibrahim Othman
- Department of Zoology, Faculty of Science, Cairo University, 12613, Giza, Egypt
| | | | - Osama Azmy
- Stem Cell Research Group, Medical Research Centre of Excellence, National Research Centre, Cairo, Egypt; Department of Reproductive Health Research, Medical Research Division, National Research Centre, Cairo, Egypt; Egypt Center for Research and Regenerative Medicine, Cairo, Egypt
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19
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Pelucchi S, Ravasi G, Piperno A. Ceruloplasmin variants might have different effects in different iron overload disorders. J Hepatol 2021; 75:1003-1004. [PMID: 34023349 DOI: 10.1016/j.jhep.2021.05.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 05/10/2021] [Indexed: 01/13/2023]
Affiliation(s)
- Sara Pelucchi
- University of Milano-Bicocca - Department of Medicine and Surgery, Monza, Italy
| | - Giulia Ravasi
- University of Milano-Bicocca - Department of Medicine and Surgery, Monza, Italy
| | - Alberto Piperno
- University of Milano-Bicocca - Department of Medicine and Surgery, Monza, Italy; Centre for Rare Diseases - Disorders of Iron Metabolism - Centre of European Reference Network (EuroBloodNet) - ASST-Monza, San Gerardo Hospital Monza, Italy; Medical Genetics - ASST-Monza, S. Gerardo Hospital Monza, Italy.
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20
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Goswami SK, Ranjan P, Dutta RK, Verma SK. Management of inflammation in cardiovascular diseases. Pharmacol Res 2021; 173:105912. [PMID: 34562603 DOI: 10.1016/j.phrs.2021.105912] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 09/01/2021] [Accepted: 09/20/2021] [Indexed: 12/12/2022]
Abstract
Cardiovascular disease is the leading cause of morbidity and mortality world-wide. Recently, the role of inflammation in the progression of diseases has significantly attracted considerable attention. In addition, various comorbidities, including diabetes, obesity, etc. exacerbate inflammation in the cardiovascular system, which ultimately leads to heart failure. Furthermore, cytokines released from specialized immune cells are key mediators of cardiac inflammation. Here, in this review article, we focused on the role of selected immune cells and cytokines (both pro-inflammatory and anti-inflammatory) in the regulation of cardiac inflammation and ultimately in cardiovascular diseases. While IL-1β, IL-6, TNFα, and IFNγ are associated with cardiac inflammation; IL-10, TGFβ, etc. are associated with resolution of inflammation and cardiac repair. IL-10 reduces cardiovascular inflammation and protects the cardiovascular system via interaction with SMAD2, p53, HuR, miR-375 and miR-21 pathway. In addition, we also highlighted recent advancements in the management of cardiac inflammation, including clinical trials of anti-inflammatory molecules to alleviate cardiovascular diseases.
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Affiliation(s)
- Sumanta Kumar Goswami
- Department of Medicine, Division of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL 35233, USA
| | - Prabhat Ranjan
- Department of Medicine, Division of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL 35233, USA
| | - Roshan Kumar Dutta
- Department of Medicine, Division of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL 35233, USA
| | - Suresh Kumar Verma
- Department of Medicine, Division of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL 35233, USA.
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21
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Luci C, Vieira E, Bourinet M, Rousseau D, Bonnafous S, Patouraux S, Lefevre L, Larbret F, Prod’homme V, Iannelli A, Tran A, Anty R, Bailly-Maitre B, Deckert M, Gual P. SYK-3BP2 Pathway Activity in Parenchymal and Myeloid Cells Is a Key Pathogenic Factor in Metabolic Steatohepatitis. Cell Mol Gastroenterol Hepatol 2021; 13:173-191. [PMID: 34411785 PMCID: PMC8593618 DOI: 10.1016/j.jcmgh.2021.08.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 08/09/2021] [Accepted: 08/10/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Spleen tyrosine kinase (SYK) signaling pathway regulates critical processes in innate immunity, but its role in parenchymal cells remains elusive in chronic liver diseases. We investigate the relative contribution of SYK and its substrate c-Abl Src homology 3 domain-binding protein-2 (3BP2) in both myeloid cells and hepatocytes in the onset of metabolic steatohepatitis. METHODS Hepatic SYK-3BP2 pathway was evaluated in mouse models of metabolic-associated fatty liver diseases (MAFLD) and in obese patients with biopsy-proven MAFLD (n = 33). Its role in liver complications was evaluated in Sh3bp2 KO and myeloid-specific Syk KO mice challenged with methionine and choline deficient diet and in homozygous Sh3bp2KI/KI mice with and without SYK expression in myeloid cells. RESULTS Here we report that hepatic expression of 3BP2 and SYK correlated with metabolic steatohepatitis severity in mice. 3BP2 deficiency and SYK deletion in myeloid cells mediated the same protective effects on liver inflammation, injury, and fibrosis priming upon diet-induced steatohepatitis. In primary hepatocytes, the targeting of 3BP2 or SYK strongly decreased the lipopolysaccharide-mediated inflammatory mediator expression and 3BP2-regulated SYK expression. In homozygous Sh3bp2KI/KI mice, the chronic inflammation mediated by the proteasome-resistant 3BP2 mutant promoted severe hepatitis and liver fibrosis with augmented liver SYK expression. In these mice, the deletion of SYK in myeloid cells was sufficient to prevent these liver lesions. The hepatic expression of SYK is also up-regulated with metabolic steatohepatitis and correlates with liver macrophages in biopsy-proven MAFLD patients. CONCLUSIONS Collectively, these data suggest an important role for the SYK-3BP2 pathway in the pathogenesis of chronic liver inflammatory diseases and highlight its targeting in hepatocytes and myeloid cells as a potential strategy to treat metabolic steatohepatitis.
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Affiliation(s)
- Carmelo Luci
- Université Côte d’Azur, INSERM, U1065, C3M, Nice, France
| | - Elodie Vieira
- Université Côte d’Azur, INSERM, U1065, C3M, Nice, France
| | - Manon Bourinet
- Université Côte d’Azur, INSERM, U1065, C3M, Nice, France
| | | | | | | | - Lauren Lefevre
- Université Côte d’Azur, INSERM, U1065, C3M, Nice, France
| | | | | | | | - Albert Tran
- Université Côte d’Azur, CHU, INSERM, U1065, C3M, Nice, France
| | - Rodolphe Anty
- Université Côte d’Azur, CHU, INSERM, U1065, C3M, Nice, France
| | | | - Marcel Deckert
- Université Côte d’Azur, INSERM, U1065, C3M, Nice, France,Marcel Deckert, PhD, Inserm UMR1065/C3M, Bâtiment Universitaire ARCHIMED, Team "Microenvironment, signaling and cancer", 151 route Saint Antoine de Ginestière, BP 2 3194, 06204 Nice, France.
| | - Philippe Gual
- Université Côte d’Azur, INSERM, U1065, C3M, Nice, France,Correspondence Address correspondence to: Philippe Gual, PhD, Inserm UMR1065/C3M, Bâtiment Universitaire ARCHIMED, Team "Chronic liver diseases associated with obesity and alcohol", 151 route Saint Antoine de Ginestière, BP 2 3194, 06204 Nice, France. fax: +33 4 89 06 42 60.
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22
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Kunz HE, Hart CR, Gries KJ, Parvizi M, Laurenti M, Dalla Man C, Moore N, Zhang X, Ryan Z, Polley EC, Jensen MD, Vella A, Lanza IR. Adipose tissue macrophage populations and inflammation are associated with systemic inflammation and insulin resistance in obesity. Am J Physiol Endocrinol Metab 2021; 321:E105-E121. [PMID: 33998291 PMCID: PMC8321823 DOI: 10.1152/ajpendo.00070.2021] [Citation(s) in RCA: 73] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Obesity is accompanied by numerous systemic and tissue-specific derangements, including systemic inflammation, insulin resistance, and mitochondrial abnormalities in skeletal muscle. Despite growing recognition that adipose tissue dysfunction plays a role in obesity-related disorders, the relationship between adipose tissue inflammation and other pathological features of obesity is not well-understood. We assessed macrophage populations and measured the expression of inflammatory cytokines in abdominal adipose tissue biopsies in 39 nondiabetic adults across a range of body mass indexes (BMI 20.5-45.8 kg/m2). Skeletal muscle biopsies were used to evaluate mitochondrial respiratory capacity, ATP production capacity, coupling, and reactive oxygen species production. Insulin sensitivity (SI) and β cell responsivity were determined from test meal postprandial glucose, insulin, c-peptide, and triglyceride kinetics. We examined the relationships between adipose tissue inflammatory markers, systemic inflammatory markers, SI, and skeletal muscle mitochondrial physiology. BMI was associated with increased adipose tissue and systemic inflammation, reduced SI, and reduced skeletal muscle mitochondrial oxidative capacity. Adipose-resident macrophage numbers were positively associated with circulating inflammatory markers, including tumor necrosis factor-α (TNFα) and C-reactive protein (CRP). Local adipose tissue inflammation and circulating concentrations of TNFα and CRP were negatively associated with SI, and circulating concentrations of TNFα and CRP were also negatively associated with skeletal muscle oxidative capacity. These results demonstrate that obese humans exhibit increased adipose tissue inflammation concurrently with increased systemic inflammation, reduced insulin sensitivity, and reduced muscle oxidative capacity and suggest that adipose tissue and systemic inflammation may drive obesity-associated metabolic derangements.NEW AND NOTEWORTHY Adipose inflammation is proposed to be at the nexus of the systemic inflammation and metabolic derangements associated with obesity. The present study provides evidence to support adipose inflammation as a central feature of the pathophysiology of obesity. Adipose inflammation is associated with systemic and peripheral metabolic derangements, including increased systemic inflammation, reduced insulin sensitivity, and reduced skeletal muscle mitochondrial respiration.
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Affiliation(s)
- Hawley E Kunz
- Endocrine Research Unit, Division of Endocrinology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Corey R Hart
- Endocrine Research Unit, Division of Endocrinology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Kevin J Gries
- Endocrine Research Unit, Division of Endocrinology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Mojtaba Parvizi
- Endocrine Research Unit, Division of Endocrinology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Marcello Laurenti
- Endocrine Research Unit, Division of Endocrinology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Chiara Dalla Man
- Biomedical Engineering and Physiology Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Rochester, Minnesota
| | - Natalie Moore
- Endocrine Research Unit, Division of Endocrinology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Xiaoyan Zhang
- Endocrine Research Unit, Division of Endocrinology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Zachary Ryan
- Endocrine Research Unit, Division of Endocrinology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Eric C Polley
- Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Michael D Jensen
- Endocrine Research Unit, Division of Endocrinology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Adrian Vella
- Endocrine Research Unit, Division of Endocrinology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Ian R Lanza
- Endocrine Research Unit, Division of Endocrinology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
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23
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Soleimani D, Parisa Moosavian S, Zolfaghari H, Paknahad Z. Effect of garlic powder supplementation on blood pressure and hs-C-reactive protein among nonalcoholic fatty liver disease patients: A randomized, double-blind, placebo-controlled trial. Food Sci Nutr 2021; 9:3556-3562. [PMID: 34262716 PMCID: PMC8269577 DOI: 10.1002/fsn3.2307] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/07/2021] [Accepted: 04/07/2021] [Indexed: 12/24/2022] Open
Abstract
Based on the anti-inflammatory and antihypertensive properties of garlic, the current study was designed to evaluate the garlic powder effects on blood pressure and high-sensitivity C-reactive protein (hs-CRP) among Nonalcoholic Fatty Liver Disease patients (NAFLD). This randomized, double-blind, placebo-controlled trial study was conducted on 110 patients with NAFLD. The patients were randomly divided into 2 groups, receiving two tablets of either 400 mg garlic or placebo daily for 15 weeks. At baseline and the end of the study, blood pressure and hs-CRP were determined. Of 110 patients enrolled in the trial, 98 subjects were included in the final analysis. After the intervention, systolic blood pressures (SBP) (mean: -7.89; 95%CI:‒11.39 to -4.39 mm Hg), diastolic blood pressure (DBP) (mean: -5.38; 95%CI: -7.77 to -3 mm Hg), and Mean Arterial Pressure (MAP) (mean: -6:95%CI: -8.4 to -3.6 mm Hg) decreased significantly in the garlic group as compared to the placebo group. Also, the percentage of reduced hs-CRP was significantly higher in the intervention group compared with the control group (mean: -16.1; 95%CI: -32.7 to -0.53; p = .035). Moreover, a positive correlation was observed between the percentage change in hs-CRP and percentage changes in SBP (r = 0.221; p = .029), DBP (r = 0.166; p = .012), and MAP (r = 0.210; p = .038). Garlic supplementation can be a safe and potentially adjunct treatment to reduce blood pressure and the risk of cardiovascular disorders in patients with NAFLD.
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Affiliation(s)
- Davood Soleimani
- Nutritional Sciences DepartmentSchool of Nutrition Sciences and Food TechnologyKermanshah University of Medical SciencesKermanshahIran
| | - Seyedeh Parisa Moosavian
- Department of Clinical NutritionSchool of Nutrition and Food SciencesIsfahan University of Medical SciencesIsfahanIran
| | - Hamid Zolfaghari
- Department of Community NutritionSchool of Nutritional Sciences and DieteticsTehran University of Medical SciencesTehranIran
| | - Zamzam Paknahad
- Department of Clinical NutritionSchool of Nutrition and Food SciencesIsfahan University of Medical SciencesIsfahanIran
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24
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Karaskova E, Velganova-Veghova M, Geryk M, Foltenova H, Kucerova V, Karasek D. Role of Adipose Tissue in Inflammatory Bowel Disease. Int J Mol Sci 2021; 22:4226. [PMID: 33921758 PMCID: PMC8073530 DOI: 10.3390/ijms22084226] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 04/05/2021] [Accepted: 04/16/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel diseases (IBDs), chronic inflammatory disorders affecting the gastrointestinal tract, include Crohn's disease and ulcerative colitis. There are increasing clinical and experimental data showing that obesity, especially visceral adiposity, plays a substantial role in the pathogenesis of IBD. Obesity seems to be an important risk factor also for IBD disease severity and clinical outcomes. Visceral adipose tissue is an active multifunctional metabolic organ involved in lipid storage and immunological and endocrine activity. Bowel inflammation penetrates the surrounding adipose tissue along the mesentery. Mesenteric fat serves as a barrier to inflammation and controls immune responses to the translocation of gut bacteria. At the same time, mesenteric adipose tissue may be the principal source of cytokines and adipokines responsible for inflammatory processes associated with IBD. This review is particularly focusing on the potential role of adipokines in IBD pathogenesis and their possible use as promising therapeutic targets.
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Affiliation(s)
- Eva Karaskova
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, 77900 Olomouc, Czech Republic; (M.V.-V.); (M.G.); (H.F.)
| | - Maria Velganova-Veghova
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, 77900 Olomouc, Czech Republic; (M.V.-V.); (M.G.); (H.F.)
| | - Milos Geryk
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, 77900 Olomouc, Czech Republic; (M.V.-V.); (M.G.); (H.F.)
| | - Hana Foltenova
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, 77900 Olomouc, Czech Republic; (M.V.-V.); (M.G.); (H.F.)
| | - Veronika Kucerova
- Department of Clinical Biochemistry, University Hospital Olomouc, 77900 Olomouc, Czech Republic;
| | - David Karasek
- Third Department of Internal Medicine—Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, 77900 Olomouc, Czech Republic;
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25
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Kuroda R, Nogawa K, Watanabe Y, Morimoto H, Sakata K, Suwazono Y. Association between High-Sensitive C-Reactive Protein and the Development of Liver Damage in Japanese Male Workers. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18062985. [PMID: 33799436 PMCID: PMC7998110 DOI: 10.3390/ijerph18062985] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 03/08/2021] [Accepted: 03/10/2021] [Indexed: 01/02/2023]
Abstract
BACKGROUND The aim of this study was to determine whether a causative relationship exists between the development of liver damage and increased high-sensitivity C-reactive protein (HsCRP) levels by long-term follow-up in Japanese workers. METHODS The target participants comprised 7830 male workers in a Japanese steel company. The prospective cohort study was performed over a 6-year period, and annual health screening information was analyzed by pooled logistic regression. The endpoint, regarded as the development of liver damage, was defined as aspartate aminotransferase (AST) ≥ 40 IU/L. RESULTS A significant relationship between the development of liver damage and increased HsCRP levels was observed after adjusting for confounding factors such as various physiological and blood chemistry parameters and lifestyle factors. The odds ratio of a 1.5-fold increase in HsCRP was 1.07 (95% confidence interval: 1.03-1.10, p < 0.001). CONCLUSIONS The results suggested that an increase of HsCRP is associated with the development of liver damage.
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Affiliation(s)
- Reiko Kuroda
- Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (R.K.); (K.N.); (Y.W.); (H.M.); (K.S.)
- Division for Environment, Health and Safety, The University of Tokyo, Tokyo 113-8654, Japan
| | - Kazuhiro Nogawa
- Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (R.K.); (K.N.); (Y.W.); (H.M.); (K.S.)
| | - Yuuka Watanabe
- Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (R.K.); (K.N.); (Y.W.); (H.M.); (K.S.)
| | - Hideki Morimoto
- Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (R.K.); (K.N.); (Y.W.); (H.M.); (K.S.)
| | - Kouichi Sakata
- Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (R.K.); (K.N.); (Y.W.); (H.M.); (K.S.)
| | - Yasushi Suwazono
- Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (R.K.); (K.N.); (Y.W.); (H.M.); (K.S.)
- Correspondence: ; Tel.: +81-43-226-2065
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Nyangasa MA, Buck C, Kelm S, Sheikh MA, Günther K, Hebestreit A. The association between leptin and inflammatory markers with obesity indices in Zanzibari children, adolescents, and adults. Obes Sci Pract 2021; 7:71-81. [PMID: 33680494 PMCID: PMC7909594 DOI: 10.1002/osp4.466] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Revised: 10/04/2020] [Accepted: 10/20/2020] [Indexed: 01/01/2023] Open
Abstract
Background Research from Western populations describes abdominal obesity as a low‐grade inflammatory disease; less is known from tropical areas with high pathogen burden. Objectives This cross‐sectional study investigated whether obesity contributes to low‐grade inflammation in 587 individuals from randomly selected households in Zanzibar. Materials and Methods The Association between obesity indices (body mass index [BMI], waist circumference [WC], and percentage body fat [%BF]), leptin, and inflammatory markers (C‐reactive protein [CRP], interleukin‐6 [IL‐6] and tumor‐necrosis factor‐α [TNF‐α]) was investigated using multinomial logistic regression analysis, accounting for ordinal outcome variables with four categories; 1st–4th quartile. Results Study participants were between 5 and 95 years; 49.6% were male. Mean serum levels were; leptin: 4.3 ± 5.2 ng/ml, CRP: 0.19 ± 0.42 µg/ml, IL‐6: 2.8 ± 5 pg/ml, and TNF‐α: 5.3 ± 5.2 pg/ml. Obesity indices were associated with leptin and CRP in the third and fourth quartiles in single models. In combined models, associations were observed between BMI (OR = 6.36 [95% CI, 1.09; 34.12]); WC (OR = 4.87 [95% CI, 1.59; 14.94]); and %BF (OR = 19.23 [95% CI, 4.70; 78.66]) and leptin in the fourth quartile; also between %BF and CRP in the third quartile (OR = 3.49 [95% CI 1.31; 9.31]). Conclusion Total body fat was associated with low‐grade inflammation in this tropical population rather than body fat distribution such as abdominal obesity. This may increase the risk of insulin resistance and other obesity‐related metabolic and cardiovascular health endpoints.
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Affiliation(s)
- Maria Adam Nyangasa
- Leibniz Institute for Prevention Research and Epidemiology-BIPS Bremen Germany
| | - Christoph Buck
- Leibniz Institute for Prevention Research and Epidemiology-BIPS Bremen Germany
| | - Soerge Kelm
- Centre for Biomolecular Interactions Bremen Faculty for Biology and Chemistry University Bremen Bremen Germany
| | - Mohammed Ali Sheikh
- Environmental Analytical Chemistry and Eco-toxicology Lab State University of Zanzibar Zanzibar Tanzania
| | - Kathrin Günther
- Leibniz Institute for Prevention Research and Epidemiology-BIPS Bremen Germany
| | - Antje Hebestreit
- Leibniz Institute for Prevention Research and Epidemiology-BIPS Bremen Germany
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Khalafi M, Symonds ME, Akbari A. The impact of exercise training versus caloric restriction on inflammation markers: a systemic review and meta-analysis. Crit Rev Food Sci Nutr 2021; 62:4226-4241. [PMID: 33506692 DOI: 10.1080/10408398.2021.1873732] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Obesity is associated with an increased risk of chronic, low-grade systematic inflammation for which exercise training (EX) and caloric restriction (CR) are potential treatments. We therefore performed a systematic meta-analysis to compare the effect of EX vs. CR and EX + CR vs. CR on inflammation markers in overweight and obese individuals. PubMed, Scopus, Web of Science and the Cochrane were searched up to April 2020 for EX vs. CR or EX + CR vs. CR interventions studies on inflammatory makers i.e. CRP, IL-6 and TNF-α in overweight and obese individuals. Standardized mean differences and 95% confidence intervals were calculated. Thirty two articles (reporting 38 trials) involving 2108 participants were included in the meta-analysis. Based on studies that directly compared EX and CR, there were no evidence for an effect of EX on IL-6 (p = 0.20) and TNF-α (p = 0.58), when compared with a CR. However, when compared to EX, CR has a statistically greater benefit on CRP (p = 0.01). In those studies, directly comparing EX + CR and CR, EX + CR caused a larger decrease in TNF-α (p = 0.002) and IL-6 (p = 0.02) and tended to decrease CRP (p = 0.06) when compared with CR. These results suggest that a combination of EX and CR may be more effective than CR alone at reducing inflammatory cytokines and CRP in overweight and obese individuals.
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Affiliation(s)
- Mousa Khalafi
- Department of Exercise Physiology, Faculty of Sport Sciences, University of Guilan, Rasht, Iran
| | - Michael E Symonds
- The Early Life Research Unit, Division of Child Health, Obstetrics and Gynaecology, and Nottingham Digestive Disease Centre and Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Amir Akbari
- Department of Exercise Physiology, Faculty of Sport Sciences, University of Guilan, Rasht, Iran
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28
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ASC, IL-18 and Galectin-3 as Biomarkers of Non-Alcoholic Steatohepatitis: A Proof of Concept Study. Int J Mol Sci 2020; 21:ijms21228580. [PMID: 33203036 PMCID: PMC7698245 DOI: 10.3390/ijms21228580] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 11/11/2020] [Accepted: 11/12/2020] [Indexed: 12/14/2022] Open
Abstract
Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease that is growing in prevalence. Symptoms of NASH become apparent when the disease has progressed significantly. Thus, there is a need to identify biomarkers of NASH in order to detect the disease earlier and to monitor disease severity. The inflammasome has been shown to play a role in liver diseases. Here, we performed a proof of concept study of biomarker analyses (cut-off points, positive and negative predictive values, receiver operating characteristic (ROC) curves, and likelihood ratios) on the serum of patients with NASH and healthy controls on apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin (IL)-18, Galectin-3 (Gal-3), and C-reactive protein (CRP). ASC, IL-18, and Gal-3 were elevated in the serum of NASH patients when compared to controls. The area under the curve (AUC) for ASC was the highest (0.7317) with an accuracy of 68%, followed by IL-18 (0.7036) with an accuracy of 66% and Gal-3 (0.6891) with an accuracy of 61%. Moreover, we then fit a stepwise multivariate logistic regression model using ASC, IL-18, and Gal-3 to determine the probability of patients having a NASH diagnosis, which resulted in an AUC of 0.71 and an accuracy of 79%, indicating that combining these biomarkers increases their diagnostic potential for NASH. These results indicate that ASC, IL-18, and Gal-3 are reliable biomarkers of NASH and that combining these analytes increases the biomarker potential of these proteins.
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29
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Wallert M, Börmel L, Lorkowski S. Inflammatory Diseases and Vitamin E-What Do We Know and Where Do We Go? Mol Nutr Food Res 2020; 65:e2000097. [PMID: 32692879 DOI: 10.1002/mnfr.202000097] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 06/26/2020] [Indexed: 12/14/2022]
Abstract
Inflammation-driven diseases and related comorbidities, such as the metabolic syndrome, obesity, fatty liver disease, and cardiovascular diseases cause significant global burden. There is a growing body of evidence that nutrients alter inflammatory responses and can therefore make a decisive contribution to the treatment of these diseases. Recently, the inflammasome, a cytosolic multiprotein complex, has been identified as a key player in inflammation and the development of various inflammation-mediated disorders, with nucleotide-binding domain and leucine-rich repeat pyrin domain (NLRP) 3 being the inflammasome of interest. Here an overview about the cellular signaling pathways underlying nuclear factor "kappa-light-chain-enhancer" of activated B-cells (NF-κB)- and NLRP3-mediated inflammatory processes, and the pathogenesis of the inflammatory diseases atherosclerosis and non-alcoholic fatty liver disease (NAFLD) is provided; next, the current state of knowledge for drug-based and dietary-based interventions for treating cardiovascular diseases and NAFLD is discussed. To date, one of the most important antioxidants in the human diet is vitamin E. Various in vitro and in vivo studies suggest that the different forms of vitamin E and also their derivatives have anti-inflammatory activity. Recent publications suggest that vitamin E-and possibly metabolites of vitamin E-are a promising therapeutic approach for treating inflammatory diseases such as NAFLD.
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Affiliation(s)
- Maria Wallert
- Department of Nutritional Biochemistry and Physiology, Institute of Nutritional Science, Friedrich Schiller University Jena, Jena, 07743, Germany.,Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Germany
| | - Lisa Börmel
- Department of Nutritional Biochemistry and Physiology, Institute of Nutritional Science, Friedrich Schiller University Jena, Jena, 07743, Germany.,Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Germany
| | - Stefan Lorkowski
- Department of Nutritional Biochemistry and Physiology, Institute of Nutritional Science, Friedrich Schiller University Jena, Jena, 07743, Germany.,Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Germany
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30
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Noordam R, Boersma V, Verkouter I, le Cessie S, Christen T, Lamb HJ, Rosendaal FR, Willems van Dijk K, van Heemst D, de Mutsert R. The role of C-reactive protein, adiponectin and leptin in the association between abdominal adiposity and insulin resistance in middle-aged individuals. Nutr Metab Cardiovasc Dis 2020; 30:1306-1314. [PMID: 32507340 DOI: 10.1016/j.numecd.2020.04.021] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Revised: 04/20/2020] [Accepted: 04/22/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS In the present study, we assessed the extent of mediation by low-grade systemic inflammation and adipokines in the association between abdominal adiposity and insulin resistance. METHODS AND RESULTS In this cross-sectional analysis of baseline measurements of the Netherlands Epidemiology of Obesity study, total body fat (TBF) was measured in all (n = 5772) participants who did not have missing data and neither used glucose-lowering medication, and abdominal subcutaneous adipose tissue (aSAT) and visceral adipose tissue (VAT) were assessed by MRI in a random subgroup (n = 2448). C-reactive protein (CRP), adiponectin, and leptin were considered as potential mediators, and insulin resistance was assessed by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Mediation by CRP, adiponectin, and leptin was studied by including the mediators to the fully adjusted linear regression model. Participants had a mean (SD) age of 56 (6) years, TBF of 36 (9) %, VAT of 119 (61) cm2 and aSAT of 300 (111) cm2. Per SD of TBF, VAT and aSAT, HOMA-IR was 64% (95% confidence interval [CI]: 59-70), 33% (95%CI: 28-42) and 20% (95%CI: 14-26) higher, respectively. The association between aSAT and HOMA-IR fully disappeared after adjustment for leptin; the association between VAT and HOMA-IR attenuated after adjustment for leptin (22%) and adiponectin (15%). No mediation was observed by CRP, and mediation estimates were similar in men and women. CONCLUSION Where leptin fully explained the aSAT-HOMA-IR association, the VAT-HOMA-IR association was only partly explained by leptin and adiponectin similarly in men and women.
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Affiliation(s)
- Raymond Noordam
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
| | - Vesna Boersma
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Inge Verkouter
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Saskia le Cessie
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Biomedical Datasciences, Leiden University Medical Center, Leiden, the Netherlands
| | - Tim Christen
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Hildo J Lamb
- Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Frits R Rosendaal
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Ko Willems van Dijk
- Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands
| | - Diana van Heemst
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
| | - Renée de Mutsert
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
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31
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Frey S, Patouraux S, Debs T, Gugenheim J, Anty R, Iannelli A. Prevalence of NASH/NAFLD in people with obesity who are currently classified as metabolically healthy. Surg Obes Relat Dis 2020; 16:2050-2057. [PMID: 32788075 DOI: 10.1016/j.soard.2020.07.009] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 06/28/2020] [Accepted: 07/03/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND While metabolic health in obesity may confer a protective status, recent studies indicate that nonalcoholic fatty liver disease (NAFLD) or even nonalcoholic steatohepatitis (NASH) may exist in this category of individuals. Although cardiovascular and diabetic risks have been well described, the risk of NAFLD and NASH among this population requires further investigation. OBJECTIVE Our goal was to compare the prevalence of steatosis, NAFLD, and NASH between individuals with metabolically healthy obesity (MHO) and individuals with metabolically abnormal obesity (MAO) and to identify preoperative risk factors for these conditions in a prospective cohort with morbid obesity scheduled for bariatric surgery. SETTINGS Tertiary referral university hospital in France. METHODS The prospective cohort included 837 bariatric patients who also had an intraoperative liver biopsy between 2002 and 2015. Obese individuals fulfilling none of the criteria in the strict definition of metabolic syndrome were considered metabolically healthy. Preoperative blood samples and liver pathology examinations were reviewed. Steatosis, NAFLD, and NASH were carefully identified allowing comparison of prevalence and risk factors between the 2 cohorts. RESULTS In total, 149 patients (17.8%) had MHO and the remaining 688 (82.2%) had MAO. The cohort with MHO was significantly younger, had a significantly lower glycosylated hemoglobin, a lower homeostasis model assessment of insulin resistance, and increased C-reactive protein. In individuals with MHO, 44 patients (29.5%) had at least moderate steatosis (>33% macrovesicular steatosis) and 5.4% had NASH. Using logistic regression, waist circumference was positively associated with NASH, whereas body mass index and alanine aminotransferase were significantly associated with severe steatosis (>66%). CONCLUSION Our study indicates that obese individuals without metabolic syndrome may develop subclinical liver involvement. Therefore, the occurrence of NAFLD and NASH in this population needs further investigation.
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Affiliation(s)
- Sébastien Frey
- Université Côte d'Azur, Nice, France; Department of Digestive surgery and liver transplantation, Archet 2 Hospital, University Hospital of Nice, Nice, France
| | - Stéphanie Patouraux
- Université Côte d'Azur, Nice, France; Department of Pathology, Pasteur Hospital, University Hospital of Nice, Nice, France
| | - Tarek Debs
- Department of Digestive surgery and liver transplantation, Archet 2 Hospital, University Hospital of Nice, Nice, France
| | - Jean Gugenheim
- Université Côte d'Azur, Nice, France; Department of Digestive surgery and liver transplantation, Archet 2 Hospital, University Hospital of Nice, Nice, France; Inserm, U1065, Team 8 "Hepatic complications of obesity and alcohol," Nice, France
| | - Rodolphe Anty
- Université Côte d'Azur, Nice, France; Inserm, U1065, Team 8 "Hepatic complications of obesity and alcohol," Nice, France; Department of Hepathology, Archet 2 Hospital, University Hospital of Nice, Nice, France
| | - Antonio Iannelli
- Université Côte d'Azur, Nice, France; Department of Digestive surgery and liver transplantation, Archet 2 Hospital, University Hospital of Nice, Nice, France; Department of Hepathology, Archet 2 Hospital, University Hospital of Nice, Nice, France.
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32
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Katsarou A, Moustakas II, Pyrina I, Lembessis P, Koutsilieris M, Chatzigeorgiou A. Metabolic inflammation as an instigator of fibrosis during non-alcoholic fatty liver disease. World J Gastroenterol 2020; 26:1993-2011. [PMID: 32536770 PMCID: PMC7267690 DOI: 10.3748/wjg.v26.i17.1993] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 04/09/2020] [Accepted: 04/21/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive storage of fatty acids in the form of triglycerides in hepatocytes. It is most prevalent in western countries and includes a wide range of clinical and histopathological findings, namely from simple steatosis to steatohepatitis and fibrosis, which may lead to cirrhosis and hepatocellular cancer. The key event for the transition from steatosis to fibrosis is the activation of quiescent hepatic stellate cells (qHSC) and their differentiation to myofibroblasts. Pattern recognition receptors (PRRs), expressed by a plethora of immune cells, serve as essential components of the innate immune system whose function is to stimulate phagocytosis and mediate inflammation upon binding to them of various molecules released from damaged, apoptotic and necrotic cells. The activation of PRRs on hepatocytes, Kupffer cells, the resident macrophages of the liver, and other immune cells results in the production of proinflammatory cytokines and chemokines, as well as profibrotic factors in the liver microenvironment leading to qHSC activation and subsequent fibrogenesis. Thus, elucidation of the inflammatory pathways associated with the pathogenesis and progression of NAFLD may lead to a better understanding of its pathophysiology and new therapeutic approaches.
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Affiliation(s)
- Angeliki Katsarou
- Department of Physiology, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
- 251 Hellenic Airforce General Hospital, Athens 11525, Greece
| | - Ioannis I Moustakas
- Department of Physiology, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Iryna Pyrina
- Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden 01307, Germany
| | - Panagiotis Lembessis
- Department of Physiology, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Michael Koutsilieris
- Department of Physiology, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Antonios Chatzigeorgiou
- Department of Physiology, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
- Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden 01307, Germany.
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Sun F, Zhao Z, Li Q, Zhou X, Li Y, Zhang H, Yan Z, He H, Ke Z, Gao Y, Li F, Tong W, Zhu Z. Detrimental Effect of C-Reactive Protein on the Cardiometabolic Cells and Its Rectifying by Metabolic Surgery in Obese Diabetic Patients. Diabetes Metab Syndr Obes 2020; 13:1349-1358. [PMID: 32425567 PMCID: PMC7195578 DOI: 10.2147/dmso.s250294] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 04/03/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND High-sensitivity C-reactive protein (hs-CRP) has been regarded as a biomarker of low-degree inflammation in illness; however, whether CRP exerts its pathogenic effect on the cardiometabolic system remains unknown. Aside from the beneficial effects of metabolic surgery on cardiometabolic system, its impact on inflammation still worth examining. Thus, this study aims to investigate the effect of CRP on adipose and vascular cells, and their responses to metabolic surgery in obese diabetic patients. PATIENTS AND METHODS The expression of CRP and RAS- and ERK-related factors in the adipocytes and VSMCs were measured. Obese patients with type 2 diabetes who underwent metabolic surgery were followed up for 2 years thereafter. Laboratory tests, which included serum hs-CRP levels and visceral fat thickness (VFT), were obtained before and after surgery. RESULTS CRP administration significantly and dose-dependently increased the intracellular-free calcium concentration ([Ca2+]i) in cultured adipocytes and in the VSMCs. CRP administration significantly increased ACE, Ang II, AT1R and p-ERK expressions, but reduced ACE2 expression in both the adipocytes and VSMCs. Clinical study showed that VFT was closely associated with serum hs-CRP. Furthermore, VFT and serum hs-CRP were found to be highly associated with blood pressure. Finally, metabolic surgery remarkably decreased blood pressure, visceral fat and serum hs-CRP levels. CONCLUSION CRP has a detrimental effect on cardiometabolic cells, aside from functioning merely as a biomarker. Serum hs-CRP levels are highly associated with hypertension and visceral obesity, which can be antagonized by metabolic surgery in obese diabetic patients.
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Affiliation(s)
- Fang Sun
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
| | - Zhigang Zhao
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
| | - Qiang Li
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
| | - Xunmei Zhou
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
| | - Yingsha Li
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
| | - Hexuan Zhang
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
| | - Zhencheng Yan
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
| | - Hongbo He
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
| | - Zhigang Ke
- Department of General Surgery, Daping Hospital, Third Military Medical University, Chongqing400042, People’s Republic of China
| | - Yu Gao
- Department of General Surgery, Daping Hospital, Third Military Medical University, Chongqing400042, People’s Republic of China
| | - Fan Li
- Department of General Surgery, Daping Hospital, Third Military Medical University, Chongqing400042, People’s Republic of China
| | - Weidong Tong
- Department of General Surgery, Daping Hospital, Third Military Medical University, Chongqing400042, People’s Republic of China
| | - Zhiming Zhu
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
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Canivet CM, Perney P, Cherick F, Orlowski M, Patouraux S, Bailly-Maitre B, Tran A, Iannelli A, Gual P, Anty R. No association between binge eating disorder and severity of non-alcoholic fatty liver disease in severely obese patients. JGH OPEN 2020; 4:525-531. [PMID: 32514465 PMCID: PMC7273712 DOI: 10.1002/jgh3.12309] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/27/2019] [Revised: 01/07/2020] [Accepted: 01/23/2020] [Indexed: 12/19/2022]
Abstract
Background and Aim The main aim of this study was to evaluate if the binge eating disorders (BEDs) related to obesity were associated with the severity of non‐alcoholic fatty liver disease (NAFLD). Methods Severely obese patients who had been referred for bariatric surgery were included in this study at the Nice University Hospital. All patients underwent a liver biopsy at the time of surgery. Between 2008 and 2015, 388 patients had an assessable Bulimia Test (BULIT) self‐questionnaire at the time of surgery. A subgroup (n = 183), between 2011 and 2015, also responded to a Beck Depression Inventory, Hospital Anxiety and Depression Scale, and a Fatigue Impact Scale autoquestionnaire. A control group of 29 healthy people matched by age and gender was included. Results Among the 388 obese patients (median age 40 years, body mass index 41.7 kg/m2, 81% women), 14 patients had a “probable diagnosis” of BED, and 47 patients had a “high risk” of developing a BED according to the BULIT. Obese patients had significantly more severe BED, depression, anxiety, and fatigue compared to controls. Steatosis, non‐alcoholic steatohepatitis, or fibrosis was not associated with BED. Similarly, the severity of NAFLD was not associated with depression, anxiety, or fatigue. Conclusions Severely obese patients had more severe BED, depression, anxiety, and fatigue than lean subjects independent of the severity of NAFLD.
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Affiliation(s)
| | - Pascal Perney
- Addiction Medicine Hospital Grau-du-Roi Nîmes France.,Paris-Saclay University, Paris-Sud University, UVSQ, CESP, U1018 Villejuif France
| | | | | | | | | | - Albert Tran
- Cote d'Azur University, Nice Hospital, INSERM, U1065, C3M Nice France
| | - Antonio Iannelli
- Cote d'Azur University, Nice Hospital, INSERM, U1065, C3M Nice France
| | | | - Rodolphe Anty
- Cote d'Azur University, Nice Hospital, INSERM, U1065, C3M Nice France
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35
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Dumas K, Ayachi C, Gilleron J, Lacas‐Gervais S, Pastor F, Favier FB, Peraldi P, Vaillant N, Yvan‐Charvet L, Bonnafous S, Patouraux S, Anty R, Tran A, Gual P, Cormont M, Tanti J, Giorgetti‐Peraldi S. REDD1 deficiency protects against nonalcoholic hepatic steatosis induced by high‐fat diet. FASEB J 2020; 34:5046-5060. [DOI: 10.1096/fj.201901799rr] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 01/24/2020] [Accepted: 01/24/2020] [Indexed: 12/11/2022]
Affiliation(s)
- Karine Dumas
- Université Côte d’Azur, Inserm, C3M, Team “Cellular and Molecular Physiopathology of Obesity” France
| | - Chaima Ayachi
- Université Côte d’Azur, Inserm, C3M, Team “Cellular and Molecular Physiopathology of Obesity” France
| | - Jerome Gilleron
- Université Côte d’Azur, Inserm, C3M, Team “Cellular and Molecular Physiopathology of Obesity” France
| | | | - Faustine Pastor
- Université Côte d’Azur, Inserm, C3M, Team “Cellular and Molecular Physiopathology of Obesity” France
| | | | - Pascal Peraldi
- Université Côte d’Azur, Inserm, CNRS, iBV, Team “Stem Cells and Differentiation” France
| | - Nathalie Vaillant
- Université Côte d’Azur, Inserm, C3M, Team “Haematometabolism in Diseases” France
| | - Laurent Yvan‐Charvet
- Université Côte d’Azur, Inserm, C3M, Team “Haematometabolism in Diseases” France
| | - Stéphanie Bonnafous
- Université Côte d’Azur, Inserm, C3M, Team “Chronic Liver Diseases Associated with Steatosis and Alcohol” France
- Université Côte d’Azur, CHU, Inserm, C3M,Team “Chronic Liver Diseases Associated with Steatosis and Alcohol” France
| | - Stéphanie Patouraux
- Université Côte d’Azur, Inserm, C3M, Team “Chronic Liver Diseases Associated with Steatosis and Alcohol” France
- Université Côte d’Azur, CHU, Inserm, C3M,Team “Chronic Liver Diseases Associated with Steatosis and Alcohol” France
| | - Rodolphe Anty
- Université Côte d’Azur, Inserm, C3M, Team “Chronic Liver Diseases Associated with Steatosis and Alcohol” France
- Université Côte d’Azur, CHU, Inserm, C3M,Team “Chronic Liver Diseases Associated with Steatosis and Alcohol” France
| | - Albert Tran
- Université Côte d’Azur, Inserm, C3M, Team “Chronic Liver Diseases Associated with Steatosis and Alcohol” France
- Université Côte d’Azur, CHU, Inserm, C3M,Team “Chronic Liver Diseases Associated with Steatosis and Alcohol” France
| | - Philippe Gual
- Université Côte d’Azur, Inserm, C3M, Team “Chronic Liver Diseases Associated with Steatosis and Alcohol” France
| | - Mireille Cormont
- Université Côte d’Azur, Inserm, C3M, Team “Cellular and Molecular Physiopathology of Obesity” France
| | - Jean‐François Tanti
- Université Côte d’Azur, Inserm, C3M, Team “Cellular and Molecular Physiopathology of Obesity” France
| | - Sophie Giorgetti‐Peraldi
- Université Côte d’Azur, Inserm, C3M, Team “Cellular and Molecular Physiopathology of Obesity” France
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Canivet CM, Bonnafous S, Rousseau D, Leclere PS, Lacas-Gervais S, Patouraux S, Sans A, Luci C, Bailly-Maitre B, Iannelli A, Tran A, Anty R, Gual P. Hepatic FNDC5 is a potential local protective factor against Non-Alcoholic Fatty Liver. Biochim Biophys Acta Mol Basis Dis 2020; 1866:165705. [PMID: 32001301 DOI: 10.1016/j.bbadis.2020.165705] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2019] [Revised: 01/09/2020] [Accepted: 01/22/2020] [Indexed: 02/06/2023]
Abstract
The proteolytic cleavage of Fibronectin type III domain-containing 5 (FNDC5) generates soluble irisin. Initially described as being mainly produced in muscle during physical exercise, irisin mediates adipose tissue thermogenesis and also regulates carbohydrate and lipid metabolism. The aim of this study was to evaluate the hepatic expression of FNDC5 and its role in hepatocytes in Non-Alcoholic Fatty Liver (NAFL). Here we report that hepatic expression of FNDC5 increased with hepatic steatosis and liver injury without impacting the systemic level of irisin in mouse models of NAFLD (HFD and MCDD) and in obese patients. The increased Fndc5 expression in fatty liver resulted from its upregulation in hepatocytes and non-parenchymal cells in mice. The local production of Fndc5 in hepatocytes was influenced by genotoxic stress and p53-dependent pathways. The down-regulation of FNDC5 in human HepG2 cells and in primary mouse hepatocytes increased the expression of PEPCK, a key enzyme involved in gluconeogenesis associated with a decrease in the expression of master genes involved in the VLDL synthesis (CIDEB and APOB). These alterations in FNDC5-silenced cells resulted to increased steatosis and insulin resistance in response to oleic acid and N-acetyl glucosamine, respectively. The downregulation of Fndc5 also sensitized primary hepatocytes to apoptosis in response to TNFα, which has been associated with decreased hepatoprotective autophagic flux. In conclusion, our human and experimental data strongly suggest that the hepatic expression of FNDC5 increased with hepatic steatosis and its upregulation in hepatocytes could dampen the development of NAFLD by negatively regulating steatogenesis and hepatocyte death.
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Affiliation(s)
- Clémence M Canivet
- Université Côte d'Azur, INSERM, U1065, C3M, Nice, France; Université Côte d'Azur, CHU, INSERM, U1065, C3M, Nice, France
| | - Stéphanie Bonnafous
- Université Côte d'Azur, INSERM, U1065, C3M, Nice, France; Université Côte d'Azur, CHU, INSERM, U1065, C3M, Nice, France
| | | | | | - Sandra Lacas-Gervais
- Université Côte d'Azur, Centre Commun de Microscopie Appliquée (CCMA), Parc Valrose, Nice, France
| | - Stéphanie Patouraux
- Université Côte d'Azur, INSERM, U1065, C3M, Nice, France; Université Côte d'Azur, CHU, INSERM, U1065, C3M, Nice, France
| | - Arnaud Sans
- Université Côte d'Azur, INSERM, U1065, C3M, Nice, France
| | - Carmelo Luci
- Université Côte d'Azur, INSERM, U1065, C3M, Nice, France
| | | | - Antonio Iannelli
- Université Côte d'Azur, INSERM, U1065, C3M, Nice, France; Université Côte d'Azur, CHU, INSERM, U1065, C3M, Nice, France
| | - Albert Tran
- Université Côte d'Azur, INSERM, U1065, C3M, Nice, France; Université Côte d'Azur, CHU, INSERM, U1065, C3M, Nice, France
| | - Rodolphe Anty
- Université Côte d'Azur, INSERM, U1065, C3M, Nice, France; Université Côte d'Azur, CHU, INSERM, U1065, C3M, Nice, France.
| | - Philippe Gual
- Université Côte d'Azur, INSERM, U1065, C3M, Nice, France.
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Anty R, Gual P. [Pathogenesis of non-alcoholic fatty liver disease]. Presse Med 2019; 48:1468-1483. [PMID: 31767252 DOI: 10.1016/j.lpm.2019.09.051] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Revised: 09/28/2019] [Accepted: 09/30/2019] [Indexed: 02/07/2023] Open
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is a complex chronic disease resulting from an interaction between genetic and environmental factors. The phenotype and pathophysiology of NAFLD is heterogeneous. NAFLD is a continuum of histological lesions of the liver from steatosis, Non-Alcoholic SteatoHepatitis (NASH), NASH with fibrosis, cirrhosis to hepatocellular carcinoma. The pathophysiology encompasses a dysfunction in fatty tissue (sub-cutaneous and visceral) associated with insulin-resistance and metabolic inflammation. NAFLD is a "multi-systemic" disease. Reciprocal and aggravating interactions exist between NAFLD, cardiovascular anomalies and diabetes. The understanding of the mechanisms responsible for NAFLD allows the identification of potential novel therapeutic targets.
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Affiliation(s)
- Rodolphe Anty
- Université Côte d'Azur, CHU, Inserm, U1065, C3M, 06000 Nice, France.
| | - Philippe Gual
- Université Côte d'Azur, Inserm, U1065, C3M, 06000 Nice, France
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Uehara D, Hayashi Y, Seki Y, Kakizaki S, Horiguchi N, Tojima H, Yamazaki Y, Sato K, Yasuda K, Yamada M, Uraoka T, Kasama K. Non-invasive prediction of non-alcoholic steatohepatitis in Japanese patients with morbid obesity by artificial intelligence using rule extraction technology. World J Hepatol 2018; 10:934-943. [PMID: 30631398 PMCID: PMC6323515 DOI: 10.4254/wjh.v10.i12.934] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 08/20/2018] [Accepted: 10/17/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To construct a non-invasive prediction algorithm for predicting non-alcoholic steatohepatitis (NASH), we investigated Japanese morbidly obese patients using artificial intelligence with rule extraction technology. METHODS Consecutive patients who required bariatric surgery underwent a liver biopsy during the operation. Standard clinical, anthropometric, biochemical measurements were used as parameters to predict NASH and were analyzed using rule extraction technology. One hundred and two patients, including 79 NASH and 23 non-NASH patients were analyzed in order to create the prediction model, another cohort with 77 patients including 65 NASH and 12 non-NASH patients were analyzed to validate the algorithm. RESULTS Alanine aminotransferase, C-reactive protein, homeostasis model assessment insulin resistance, albumin were extracted as predictors of NASH using a recursive-rule extraction algorithm. When we adopted the extracted rules for the validation cohort using a highly accurate rule extraction algorithm, the predictive accuracy was 79.2%. The positive predictive value, negative predictive value, sensitivity and specificity were 88.9%, 35.7%, 86.2% and 41.7%, respectively. CONCLUSION We successfully generated a useful model for predicting NASH in Japanese morbidly obese patients based on their biochemical profile using a rule extraction algorithm.
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Affiliation(s)
- Daisuke Uehara
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
| | - Yoichi Hayashi
- Department of Computer Science, Meiji University, Tama-ku, Kawasaki, Kanagawa 214-8571, Japan
| | - Yosuke Seki
- Weight Loss and Metabolic Surgery Center, Yotsuya Medical Cube, Tokyo 102-0084, Japan
| | - Satoru Kakizaki
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
| | - Norio Horiguchi
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
| | - Hiroki Tojima
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
| | - Yuichi Yamazaki
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
| | - Ken Sato
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
| | - Kazuki Yasuda
- Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
| | - Masanobu Yamada
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
| | - Toshio Uraoka
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
| | - Kazunori Kasama
- Weight Loss and Metabolic Surgery Center, Yotsuya Medical Cube, Tokyo 102-0084, Japan
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Keinänen J, Suvisaari J, Reinikainen J, Kieseppä T, Lindgren M, Mäntylä T, Rikandi E, Sundvall J, Torniainen-Holm M, Mantere O. Low-grade inflammation in first-episode psychosis is determined by increased waist circumference. Psychiatry Res 2018; 270:547-553. [PMID: 30343240 DOI: 10.1016/j.psychres.2018.10.022] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Revised: 09/26/2018] [Accepted: 10/08/2018] [Indexed: 10/28/2022]
Abstract
Psychosis is associated with low-grade inflammation as measured by high-sensitivity C-reactive protein (hs-CRP), a risk factor for cardiovascular events and mortality in the general population. We investigated the relationship between hs-CRP and anthropometric and metabolic changes in first-episode psychosis (FEP) during the first treatment year. We recruited 95 FEP patients and 62 controls, and measured longitudinal changes in hs-CRP, weight, waist circumference, insulin resistance, and lipids. We used linear mixed models to analyze the longitudinal relationship between hs-CRP and clinical, anthropometric and metabolic measures. At baseline, patients with FEP had higher levels of insulin resistance, total and low-density lipoprotein cholesterol, apolipoprotein B, and triglycerides. Baseline weight, waist circumference, hs-CRP, fasting glucose, and high-density lipoprotein cholesterol were similar between patients and controls. Marked increases in anthropometric measures and hs-CRP were observed in FEP during the 12-month follow-up. However, glucose and lipid parameters did not change significantly. In the mixed models, waist circumference and female sex were significant predictors of hs-CRP levels in FEP. Prevention of the early development of abdominal obesity in FEP is crucial, as abdominal obesity is accompanied by chronic low-grade inflammation, which increases further the cardiovascular risk in this vulnerable population.
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Affiliation(s)
- Jaakko Keinänen
- Department of Public Health Solutions, Mental Health Unit, National Institute for Health and Welfare, P.O. Box 30, FIN-00271 Helsinki, Finland; Faculty of Medicine, Department of Psychiatry, University of Helsinki, P.O. Box 590, FIN-00029 Helsinki, Finland.
| | - Jaana Suvisaari
- Department of Public Health Solutions, Mental Health Unit, National Institute for Health and Welfare, P.O. Box 30, FIN-00271 Helsinki, Finland
| | - Jaakko Reinikainen
- Department of Public Health Solutions, Public Health Evaluation and Projection Unit, National Institute for Health and Welfare, P.O. Box 30, FIN-00271 Helsinki, Finland
| | - Tuula Kieseppä
- Psychiatry, University of Helsinki and Helsinki University Hospital, P.O. Box 590, FIN-00029 Helsinki, Finland
| | - Maija Lindgren
- Department of Public Health Solutions, Mental Health Unit, National Institute for Health and Welfare, P.O. Box 30, FIN-00271 Helsinki, Finland
| | - Teemu Mäntylä
- Department of Public Health Solutions, Mental Health Unit, National Institute for Health and Welfare, P.O. Box 30, FIN-00271 Helsinki, Finland; Faculty of Medicine, Department of Psychology and Logopedics, University of Helsinki, P.O. Box 63, FIN-00014 Helsinki, Finland
| | - Eva Rikandi
- Department of Public Health Solutions, Mental Health Unit, National Institute for Health and Welfare, P.O. Box 30, FIN-00271 Helsinki, Finland; Faculty of Medicine, Department of Psychology and Logopedics, University of Helsinki, P.O. Box 63, FIN-00014 Helsinki, Finland
| | - Jouko Sundvall
- Department of Public Health Solutions, Genomics and Biomarkers Unit, National Institute for Health and Welfare, P.O. Box 30, FIN-00271 Helsinki, Finland
| | - Minna Torniainen-Holm
- Department of Public Health Solutions, Mental Health Unit, National Institute for Health and Welfare, P.O. Box 30, FIN-00271 Helsinki, Finland
| | - Outi Mantere
- Psychiatry, University of Helsinki and Helsinki University Hospital, P.O. Box 590, FIN-00029 Helsinki, Finland; Department of Psychiatry, McGill University, 1033 Pine Avenue West, QC, H3A 1A1 Montréal, Canada; Bipolar Disorders Clinic, Douglas Mental Health University Institute, 6875 LaSalle Boulevard, QC, H4H 1R3 Montréal, Canada
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Lebeaupin C, Vallée D, Hazari Y, Hetz C, Chevet E, Bailly-Maitre B. Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease. J Hepatol 2018; 69:927-947. [PMID: 29940269 DOI: 10.1016/j.jhep.2018.06.008] [Citation(s) in RCA: 640] [Impact Index Per Article: 91.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Revised: 05/22/2018] [Accepted: 06/14/2018] [Indexed: 12/13/2022]
Abstract
The global epidemic of obesity has been accompanied by a rising burden of non-alcoholic fatty liver disease (NAFLD), with manifestations ranging from simple steatosis to non-alcoholic steatohepatitis, potentially developing into hepatocellular carcinoma. Although much attention has focused on NAFLD, its pathogenesis remains largely obscure. The hallmark of NAFLD is the hepatic accumulation of lipids, which subsequently leads to cellular stress and hepatic injury, eventually resulting in chronic liver disease. Abnormal lipid accumulation often coincides with insulin resistance in steatotic livers and is associated with perturbed endoplasmic reticulum (ER) proteostasis in hepatocytes. In response to chronic ER stress, an adaptive signalling pathway known as the unfolded protein response is triggered to restore ER proteostasis. However, the unfolded protein response can cause inflammation, inflammasome activation and, in the case of non-resolvable ER stress, the death of hepatocytes. Experimental data suggest that the unfolded protein response influences hepatic tumour development, aggressiveness and response to treatment, offering novel therapeutic avenues. Herein, we provide an overview of the evidence linking ER stress to NAFLD and discuss possible points of intervention.
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Affiliation(s)
| | - Deborah Vallée
- Université Côte d'Azur, INSERM, U1065, C3M, 06200 Nice, France
| | - Younis Hazari
- Biomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile
| | - Claudio Hetz
- Biomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; Buck Institute for Research on Aging, Novato, CA 94945, USA; Department of Immunology and Infectious Diseases, Harvard School of Public Health, 02115 Boston, MA, USA
| | - Eric Chevet
- "Chemistry, Oncogenesis, Stress, Signaling", Inserm U1242, Université de Rennes, Rennes, France; Centre de Lutte Contre le Cancer Eugène Marquis, Rennes, France
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C-reactive protein expression in adipose tissue of children with acute appendicitis. Pediatr Res 2018; 84:564-567. [PMID: 29991774 DOI: 10.1038/s41390-018-0091-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Revised: 04/12/2018] [Accepted: 06/01/2018] [Indexed: 11/08/2022]
Abstract
OBJECTIVE The aim of this study is to gain insights into the role of visceral adipose tissue as a source of C-reactive protein (CRP) in acute inflammation and to explore the potential relationship of CRP expression with the severity of appendicitis. METHODS A total of 20 pediatric patients undergoing appendectomy were included in the study. Patients were divided into two groups according to appendicitis severity (uncomplicated and complicated). CRP levels were measured in visceral fat samples by western blotting, as well as in serum by biochemical testing. RESULTS CRP was found to be expressed in visceral adipose tissue. The adipose tissue of patients with complicated appendicitis showed significantly higher CRP levels (p = 0.002) compared to patients with uncomplicated appendicitis. These results mirrored the CRP values obtained in serum (p = 0.018). CONCLUSION In childhood, visceral adipose tissue is a source of CRP in acute inflammation, and its expression is potentially associated with the severity of local inflammation.
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Occlusion phenomenon of redox probe by protein as a way of voltammetric detection of non-electroactive C-reactive protein. Biosens Bioelectron 2018; 117:232-239. [DOI: 10.1016/j.bios.2018.06.019] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Revised: 05/16/2018] [Accepted: 06/07/2018] [Indexed: 11/18/2022]
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Sagae SC, Zanardini B, Ribeiro-Paz ED, Amaral AC, Bronczek GA, Lubaczeuski C, Grassiolli S, Koehler-Santos P, de Oliveira JR, Donadio MVF, Raineki C. Metabolic dysfunction in a rat model of early-life scarcity-adversity: Modulatory role of cafeteria diet. Exp Physiol 2018; 103:1481-1493. [PMID: 30211444 DOI: 10.1113/ep087171] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Accepted: 09/12/2018] [Indexed: 12/11/2022]
Abstract
NEW FINDINGS What is the central question of this study? Early-life adversity is associated with increased risk for obesity and metabolic dysfunction. However, it is unclear whether obesity and metabolic dysfunction result from coping strategies to deal with adversity-related emotional dysregulation, a direct programming of systems regulating metabolic function, or a combination of both. What is the main finding and its importance? Early-life adversity increases vulnerability to later-life obesity and metabolic dysfunction, indicating that genetics and adult lifestyle are not the only determinants of obesity and related metabolic dysfunction. Moreover, consumption of cafeteria diet exacerbated metabolic dysfunction associated with early-life adversity, suggesting that poor dietary choices might have a bigger impact in the context of early-life adversity. ABSTRACT Early-life adversity has become recognized as an important factor contributing to adult obesity and associated metabolic dysfunction. However, it is unclear whether obesity and metabolic dysfunction associated with early-life adversity result from coping strategies to deal with adversity-related emotional dysregulation, a direct programming of systems regulating metabolic function, or a combination. Interestingly, both early-life adversity and later-life dietary choices affect immune function, favouring pro-inflammatory mechanisms that are associated with obesity-related metabolic dysfunction. To investigate the unique and/or interactive effects of early-life adversity and later-life dietary choices for increased vulnerability to obesity and metabolic dysfunction, and specifically the role of the immune system in this vulnerability, we combined a naturalistic rat model of early-life scarcity-adversity with a rat model of obesity, the cafeteria diet. Our results indicate that early-life adversity alone induces insulin resistance, reduces pancreatic insulin secretion, plasma concentrations of triglycerides and cholesterol, and increases fasting glucose and tumour necrosis factor-α plasma concentrations. Importantly, animals exposed to adverse rearing were more vulnerable to metabolic dysregulation associated with the cafeteria diet, given that they consumed more energy, showed more severe hepatic steatosis and increased concentrations of the pro-inflammatory cytokine interleukin-1β than normally reared animals fed the cafeteria diet. Together, our results suggest that early-life adversity negatively programmes physiological systems that regulate metabolic function and increases vulnerability to obesity and metabolic dysfunction in adulthood. These results highlight the intrinsic relationship between the quality of the early postnatal environment and later-life dietary choices on adult health outcomes.
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Affiliation(s)
- Sara C Sagae
- Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil
| | - Bárbara Zanardini
- Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil
| | - Edson D Ribeiro-Paz
- Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil
| | - Ana Claudia Amaral
- Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil
| | - Gabriela A Bronczek
- Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil
| | - Camila Lubaczeuski
- Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil
| | - Sabrina Grassiolli
- Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil
| | - Patrícia Koehler-Santos
- Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
| | - Jarbas Rodrigues de Oliveira
- Centro Infant, Institute of Biomedical Research (IPB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Márcio Vinícius Fagundes Donadio
- Laboratório de Biofísica Celular e Inflamação, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Charlis Raineki
- Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada
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Moore BF, Sauder KA, Starling AP, Hebert JR, Shivappa N, Ringham BM, Glueck DH, Dabelea D. Proinflammatory Diets during Pregnancy and Neonatal Adiposity in the Healthy Start Study. J Pediatr 2018; 195:121-127.e2. [PMID: 29217099 PMCID: PMC6363107 DOI: 10.1016/j.jpeds.2017.10.030] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Revised: 09/26/2017] [Accepted: 10/12/2017] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To evaluate the association between dietary inflammatory index (DII) scores during pregnancy and neonatal adiposity. STUDY DESIGN The analysis included 1078 mother-neonate pairs in Healthy Start, a prospective prebirth cohort. Diet was assessed using repeated 24-hour dietary recalls. DII scores were obtained by summing nutrient intakes, which were standardized to global means and multiplied by inflammatory effect scores. Air displacement plethysmography measured fat mass and fat-free mass within 72 hours of birth. Linear and logistic models evaluated the associations of DII scores with birth weight, fat mass, fat-free mass, and percent fat mass, and with categorical outcomes of small- and large-for-gestational age. We tested for interactions with prepregnancy BMI and gestational weight gain. RESULTS The interaction between prepregnancy BMI and DII was statistically significant for birth weight, neonatal fat mass, and neonatal percent fat mass. Among neonates born to obese women, each 1-unit increase in DII was associated with increased birth weight (53 g; 95% CI, 20, 87), fat mass (20 g; 95% CI, 7-33), and percent fat mass (0.5%; 95% CI, 0.2-0.8). No interaction was detected for small- and large-for-gestational age. Each 1-unit increase in DII score was associated a 40% increase in odds of a large-for-gestational age neonate (1.4; 95% CI, 1.0-2.0; P = .04), but not a small-for-gestational age neonate (1.0; 95% CI, 0.8-1.2; P = .80). There was no evidence of an interaction with gestational weight gain. CONCLUSIONS Our findings support the hypothesis that an increased inflammatory milieu during pregnancy may be a risk factor for neonatal adiposity. TRIAL REGISTRATION Clinicaltrials.gov: NCT02273297.
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Affiliation(s)
- Brianna F Moore
- Department of Epidemiology, Colorado School of Public Health, Aurora CO, USA
| | - Katherine A Sauder
- Department of Pediatrics, University of Colorado School of Medicine, Aurora CO, USA
| | - Anne P Starling
- Department of Epidemiology, Colorado School of Public Health, Aurora CO, USA
| | - James R Hebert
- Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA,Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA,Connecting Health Innovations, LLC, Columbia, SC
| | - Nitin Shivappa
- Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA,Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA,Connecting Health Innovations, LLC, Columbia, SC
| | - Brandy M Ringham
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora CO, USA
| | - Deborah H Glueck
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora CO, USA
| | - Dana Dabelea
- Department of Epidemiology, Colorado School of Public Health, Aurora, CO; Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO.
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Klyne DM, Barbe MF, van den Hoorn W, Hodges PW. ISSLS PRIZE IN CLINICAL SCIENCE 2018: longitudinal analysis of inflammatory, psychological, and sleep-related factors following an acute low back pain episode-the good, the bad, and the ugly. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2018; 27:763-777. [PMID: 29460011 DOI: 10.1007/s00586-018-5490-7] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/18/2018] [Accepted: 01/20/2018] [Indexed: 02/07/2023]
Abstract
STUDY DESIGN Prospective longitudinal study. OBJECTIVE To determine whether systemic cytokines and C-reactive protein (CRP) during an acute episode of low back pain (LBP) differ between individuals who did and did not recover by 6 months and to identify sub-groups based on patterns of inflammatory, psychological, and sleep features associated with recovery/non-recovery. Systemic inflammation is observed in chronic LBP and may contribute to the transition from acute to persistent LBP. Longitudinal studies are required to determine whether changes present early or develop over time. Psychological and/or sleep-related factors may be related. METHODS Individuals within 2 weeks of onset of acute LBP (N = 109) and pain-free controls (N = 55) provided blood for assessment of CRP, tumor necrosis factor (TNF), interleukin-6 (IL-6) and interleukin-1β, and completed questionnaires related to pain, disability, sleep, and psychological status. LBP participants repeated measurements at 6 months. Biomarkers were compared between LBP and control participants at baseline, and in longitudinal (baseline/6 months) analysis, between unrecovered (≥pain and disability), partially recovered (reduced pain and/or disability) and recovered (no pain and disability) participants at 6 months. We assessed baseline patterns of inflammatory, psychological, sleep, and pain data using hierarchical clustering and related the clusters to recovery (% change in pain) at 6 months. RESULTS CRP was higher in acute LBP than controls at baseline. In LBP, baseline CRP was higher in the recovered than non-recovered groups. Conversely, TNF was higher at both time-points in the non-recovered than recovered groups. Two sub-groups were identified that associated with more ("inflammatory/poor sleep") or less ("high TNF/depression") recovery. CONCLUSIONS This is the first evidence of a relationship between an "acute-phase" systemic inflammatory response and recovery at 6 months. High inflammation (CRP/IL-6) was associated with good recovery, but specific elevation of TNF, along with depressive symptoms, was associated with bad recovery. Depression and TNF may have a two-way relationship. These slides can be retrieved under Electronic Supplementary Material.
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Affiliation(s)
- David M Klyne
- NHMRC Centre of Clinical Research Excellence in Spinal Pain, Injury and Health, School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia
| | - Mary F Barbe
- Department of Anatomy and Cell Biology, Temple University School of Medicine, Temple University, Philadelphia, USA
| | - Wolbert van den Hoorn
- NHMRC Centre of Clinical Research Excellence in Spinal Pain, Injury and Health, School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia
| | - Paul W Hodges
- NHMRC Centre of Clinical Research Excellence in Spinal Pain, Injury and Health, School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia.
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Anty R, Hastier A, Canivet CM, Patouraux S, Schneck AS, Ferrari-Panaia P, Ben-Amor I, Saint-Paul MC, Gugenheim J, Gual P, Iannelli A, Tran A. Severe Vitamin D Deficiency Is Not Associated with Liver Damage in Morbidly Obese Patients. Obes Surg 2018; 26:2138-2143. [PMID: 26787197 DOI: 10.1007/s11695-016-2070-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS A deficiency in vitamin D could be deleterious during chronic liver diseases. However, contradictory data have been published in patients with non-alcoholic fatty liver disease. The aim of the study was to compare the blood level of 25 hydroxy vitamin D (25-OH vitamin D) with the severity of liver lesions, in a large cohort of morbidly obese patients. PATIENTS AND METHOD Three hundred ninety-eight morbidly obese patients had a liver biopsy. The non-alcoholic steatohepatitis (NASH) Clinical Research Network Scoring System Definition and Scores were used. 25-OH vitamin D was evaluated with a Diasorin®Elisa Kit. Logistic regression analyses were performed to obtain predictive factors of the severity of liver histology. RESULTS 20.6 % of patients had NASH. The stage of fibrosis was F0 12.9 %, F1 57.36 %, F2 25.32 %, F3 (bridging fibrosis) 3.88 %, and F4 (cirrhosis) 0.52 %. The 25-OH vitamin D level inversely correlated to the NAS (r = 0.12 and p = 0.01) and to steatosis (r = 0.14 and p = 0.007); however, it was not associated with the presence of NASH. The level of vitamin D was significantly lower in patients with significant fibrosis compared to those without (15.9 (11.1-23.5) vs 19.6 (13.7-24.7) ng/ml, p = 0.02). There was an inverse correlation between the severity of fibrosis and the values of 25-OH vitamin D (r = 0.12 and p = 0.01). In a logistic regression analysis, no parameters were independently associated with the severity of fibrosis except the presence of steatohepatitis (1.94 (1.13-3.35) p = 0.017). CONCLUSION Low levels of 25-OH vitamin D were not independently associated with liver damage in morbidly obese patients with non-alcoholic fatty liver diseases (NAFLD).
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Affiliation(s)
- Rodolphe Anty
- Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, Team 8, "Hepatic Complications in Obesity", Nice, F-06204, Cedex 3, France. .,Pôle Référence Hépatite C, Hôpital de l'Archet 2, Centre Hospitalier Universitaire of Nice, 151, Route Saint-Antoine de Ginestière, BP 3079, F-06202, Nice, Cedex 3, France. .,Faculty of Medecine, University of Nice-Sophia-Antipolis, Nice, F-06107, Cedex 2, France.
| | - Audrey Hastier
- Pôle Référence Hépatite C, Hôpital de l'Archet 2, Centre Hospitalier Universitaire of Nice, 151, Route Saint-Antoine de Ginestière, BP 3079, F-06202, Nice, Cedex 3, France
| | - Clémence M Canivet
- Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, Team 8, "Hepatic Complications in Obesity", Nice, F-06204, Cedex 3, France.,Pôle Référence Hépatite C, Hôpital de l'Archet 2, Centre Hospitalier Universitaire of Nice, 151, Route Saint-Antoine de Ginestière, BP 3079, F-06202, Nice, Cedex 3, France.,Faculty of Medecine, University of Nice-Sophia-Antipolis, Nice, F-06107, Cedex 2, France
| | - Stéphanie Patouraux
- Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, Team 8, "Hepatic Complications in Obesity", Nice, F-06204, Cedex 3, France.,Faculty of Medecine, University of Nice-Sophia-Antipolis, Nice, F-06107, Cedex 2, France.,Biological Centre, Centre Hospitalier Universitaire of Nice, Nice, F-06107, Cedex 2, France
| | - Anne-Sophie Schneck
- Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, Team 8, "Hepatic Complications in Obesity", Nice, F-06204, Cedex 3, France.,Pôle Référence Hépatite C, Hôpital de l'Archet 2, Centre Hospitalier Universitaire of Nice, 151, Route Saint-Antoine de Ginestière, BP 3079, F-06202, Nice, Cedex 3, France.,Faculty of Medecine, University of Nice-Sophia-Antipolis, Nice, F-06107, Cedex 2, France
| | | | - Imed Ben-Amor
- Pôle Référence Hépatite C, Hôpital de l'Archet 2, Centre Hospitalier Universitaire of Nice, 151, Route Saint-Antoine de Ginestière, BP 3079, F-06202, Nice, Cedex 3, France
| | | | - Jean Gugenheim
- Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, Team 8, "Hepatic Complications in Obesity", Nice, F-06204, Cedex 3, France.,Pôle Référence Hépatite C, Hôpital de l'Archet 2, Centre Hospitalier Universitaire of Nice, 151, Route Saint-Antoine de Ginestière, BP 3079, F-06202, Nice, Cedex 3, France.,Faculty of Medecine, University of Nice-Sophia-Antipolis, Nice, F-06107, Cedex 2, France
| | - Philippe Gual
- Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, Team 8, "Hepatic Complications in Obesity", Nice, F-06204, Cedex 3, France.,Faculty of Medecine, University of Nice-Sophia-Antipolis, Nice, F-06107, Cedex 2, France
| | - Antonio Iannelli
- Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, Team 8, "Hepatic Complications in Obesity", Nice, F-06204, Cedex 3, France.,Pôle Référence Hépatite C, Hôpital de l'Archet 2, Centre Hospitalier Universitaire of Nice, 151, Route Saint-Antoine de Ginestière, BP 3079, F-06202, Nice, Cedex 3, France.,Faculty of Medecine, University of Nice-Sophia-Antipolis, Nice, F-06107, Cedex 2, France
| | - Albert Tran
- Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, Team 8, "Hepatic Complications in Obesity", Nice, F-06204, Cedex 3, France.,Pôle Référence Hépatite C, Hôpital de l'Archet 2, Centre Hospitalier Universitaire of Nice, 151, Route Saint-Antoine de Ginestière, BP 3079, F-06202, Nice, Cedex 3, France.,Faculty of Medecine, University of Nice-Sophia-Antipolis, Nice, F-06107, Cedex 2, France
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Sarma SM, Singh DP, Singh P, Khare P, Mangal P, Singh S, Bijalwan V, Kaur J, Mantri S, Boparai RK, Mazumder K, Bishnoi M, Bhutani KK, Kondepudi KK. Finger millet arabinoxylan protects mice from high-fat diet induced lipid derangements, inflammation, endotoxemia and gut bacterial dysbiosis. Int J Biol Macromol 2018; 106:994-1003. [DOI: 10.1016/j.ijbiomac.2017.08.100] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2017] [Revised: 08/14/2017] [Accepted: 08/16/2017] [Indexed: 02/08/2023]
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Gómez-Abril SÁ, Morillas-Ariño C, Ponce-Marco JL, Torres-Sánchez T, Delgado-Gomis F, Hernández-Mijares A, Rocha M. Short- and Long-Term Effects of Weight Loss on the Complement Component C3 After Laparoscopic Gastric Bypass in Obese Patients. Obes Surg 2017; 26:2756-2763. [PMID: 27143095 DOI: 10.1007/s11695-016-2195-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND The C3 complement component (C3c) is increasingly recognized as a cardiometabolic risk factor, but how it is affected after weight loss through gastric bypass is a question yet to be answered. METHODS A total of 66 obese patients underwent laparoscopic gastric bypass. Anthropometric parameters, total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), glucose, insulin, HOMA-IR, liver enzymes, high-sensitivity C-reactive protein (hsCRP), and C3c levels were evaluated at baseline and at 1 and 5 years post-surgery. RESULTS All anthropometric and biochemical parameters improved significantly after surgery, although a deterioration was detected with respect to the percentage of excess of weight loss, insulin, TC, LDLc, and lactate dehydrogenase 5 years post-surgery. Despite this, a remission rate of 84 % was observed in the presence of metabolic syndrome after 5 years follow-up. hsCRP and C3c were reduced significantly after surgery and maintained throughout the experimental period. In addition, C3c was correlated with BMI and insulin at all time points. The multivariate regression model, in which C3c was a dependent variable, revealed that aspartate aminotransferase and BMI were independent variables at baseline, alkaline phosphatase and insulin were independent at 1 year post-surgery, and insulin, BMI, and TC were independent at 5 years post-surgery. CONCLUSIONS C3c may be a marker of the chronic inflammatory process underlying insulin resistance. Its association with BMI and liver enzymes supports a major role in metabolic activity, although future research is needed to clarify the nature of the molecular mechanisms involved and the physiological significance of these findings.
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Affiliation(s)
- Segundo Á Gómez-Abril
- Department of General and Digestive Surgery, University Hospital Doctor Peset-FISABIO, Valencia, Spain
| | - Carlos Morillas-Ariño
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Av. Gaspar, Aguilar 90, 46017, Valencia, Spain
| | - Jose L Ponce-Marco
- Department of General and Digestive Surgery, University Hospital La Fe, Valencia, Spain
| | - Teresa Torres-Sánchez
- Department of General and Digestive Surgery, University Hospital Doctor Peset-FISABIO, Valencia, Spain
| | - Fernando Delgado-Gomis
- Department of General and Digestive Surgery, University Hospital Doctor Peset-FISABIO, Valencia, Spain
| | - Antonio Hernández-Mijares
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Av. Gaspar, Aguilar 90, 46017, Valencia, Spain. .,Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain. .,Department of Medicine, University of Valencia, Valencia, Spain.
| | - Milagros Rocha
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Av. Gaspar, Aguilar 90, 46017, Valencia, Spain. .,Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain. .,CIBER CB06/04/0071 Research Group, CIBER Hepatic and Digestive Diseases, University of Valencia, Av Blasco Ibáñez 15, 46010, Valencia, Spain.
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Yan PJ, Xu Y, Wan Q, Feng J, Li H, Gao CL, Yang J, Zhong HH, Zhang ZH. Decreased plasma neuregulin 4 concentration is associated with increased high-sensitivity C-reactive protein in newly diagnosed type 2 diabetes mellitus patients: a cross-sectional study. Acta Diabetol 2017; 54:1091-1099. [PMID: 28918492 DOI: 10.1007/s00592-017-1044-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2017] [Accepted: 08/21/2017] [Indexed: 12/18/2022]
Abstract
AIMS Inflammation has been reported to be involved in the pathogenesis of atherosclerosis. This principal objective of this study was to investigate if the secretion of neuregulin 4 (Nrg4), a soluble protein associated with metabolic syndrome and subclinical cardiovascular disease, is correlated with the inflammation marker high-sensitivity C-reactive protein (hs-CRP) in patients with newly diagnosed type 2 diabetes mellitus (nT2DM). METHODS A study group of 311 nT2DM patients was divided into three subgroups based on hs-CRP tertiles. Multiple linear regression was conducted to explore the association between plasma Nrg4 and hs-CRP levels. RESULTS The nT2DM patients with the highest hs-CRP levels (>2.46 mg/L) exhibited higher atherogenic coefficients and atherogenic index of plasma (AIP) levels, but lower levels of plasma Nrg4, as compared to those with the lowest hs-CRP levels (<0.63 mg/L). Plasma Nrg4 levels were inversely associated with white blood cell count, hs-CRP, and AIP and positively associated with high-density lipoprotein cholesterol (HDL-C), before and after adjustment for age, gender, body mass index (BMI), and body fat percentage (P < 0.01 or P < 0.05). hs-CRP was the factor most strongly associated with plasma Nrg4 levels. CONCLUSIONS These results indicate that lower plasma Nrg4 levels may be associated with elevated hs-CRP in nT2DM patients. It generates the hypothesis that decreased levels of Nrg4 may trigger the development of atherosclerosis through its proinflammatory effects. These findings need to be confirmed by further prospective studies.
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Affiliation(s)
- Pi-Jun Yan
- Department of Endocrinology, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Yong Xu
- Department of Endocrinology, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Qin Wan
- Department of Endocrinology, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Jian Feng
- Department of Cardiovascular Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Hua Li
- Department of Endocrinology, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Chen-Lin Gao
- Department of Endocrinology, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Jun Yang
- Department of Endocrinology, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Hai-Hua Zhong
- Department of Endocrinology, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Zhi-Hong Zhang
- Department of General Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
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Coimbra S, Ferreira C, Belo L, Rocha-Pereira P, Catarino A, Monteiro L, Catarino C, Santos-Silva A. Impact of weight loss on inflammation and red blood cell biomarkers after laparoscopic gastric banding surgery. J Investig Med 2017; 66:304-308. [DOI: 10.1136/jim-2017-000528] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/24/2017] [Indexed: 01/12/2023]
Abstract
Adipose tissue produces several adipokines that are enrolled in different metabolic and inflammatory pathways that may disturb iron metabolism and erythropoiesis. Considering that laparoscopic adjustable gastric banding (LAGB) has not been associated with a long-term risk of malabsorption, we performed a 13-month follow-up study in severe obese patients submitted to LAGB in order to clarify its impact on inflammation, iron metabolism and on red blood cell (RBC) biomarkers. Twenty obese patients were enrolled in the study, being clinical and analytically assessed before (T0) and 13 months after LAGB intervention (T1). Inflammation, iron bioavailability and RBC biomarkers were evaluated at T0 and T1. At T1, weight and anthropometric indices decreased significantly; patients showed a significant increase in mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration (MCHC), and a reduction in red cell distribution width, ferritin, hepcidin, tumor necrosis factor-α, interleukin-6 (IL-6) and C-reactive protein. Before LAGB, IL-6 correlated negatively with iron, hemoglobin concentration and MCHC; hepcidin correlated inversely with transferrin. Our data show that 13 months after LAGB, the weight loss is associated with an improvement in inflammation, namely a reduction in IL-6 that may reduce hepcidin production, improving iron availability for erythropoiesis, as shown by more adequate erythrocyte hemoglobinization.
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