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Sinton MC, Kajimura S. From fat storage to immune hubs: the emerging role of adipocytes in coordinating the immune response to infection. FEBS J 2025; 292:1868-1883. [PMID: 39428707 PMCID: PMC12001177 DOI: 10.1111/febs.17302] [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: 06/14/2024] [Revised: 08/21/2024] [Accepted: 10/04/2024] [Indexed: 10/22/2024]
Abstract
Adipose tissue is a rich source of diverse cell populations, including immune cells, adipocytes and stromal cells. Interactions between these different cell types are now appreciated to be critical for maintaining tissue structure and function, by governing processes such as adipogenesis, lipolysis and differentiation of white to beige adipocytes. Interactions between these cells also drive inflammation in obesity, leading to an expansion of adipose tissue immune cells, and the secretion of proinflammatory cytokines from immune cells and from adipocytes themselves. However, in evolutionary terms, obesity is a recent phenomenon, raising the question of why adipocytes evolved to express factors that influence the immune response. Studies of various pathogens indicate that adipocytes are highly responsive to infection, altering their metabolic profiles in a way that can be used to release nutrients and fuel the immune response. In the case of infection with the extracellular parasite Trypanosoma brucei, attenuating the ability of adipocytes to sense the cytokine IL-17 results in a loss of control of the local immune response and an increased pathogen load. Intriguingly, comparisons of the adipocyte response to infection suggest that the immune responses of these cells occur in a pathogen-dependent manner, further confirming their complexity. Here, with a focus on murine adipose tissue, we discuss the emerging concept that, in addition to their canonical function, adipocytes are immune signalling hubs that integrate and disseminate signals from the immune system to generate a local environment conducive to pathogen clearance.
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Affiliation(s)
- Matthew C. Sinton
- Division of Immunology, Immunity to Infection and Respiratory MedicineUniversity of ManchesterUK
- Lydia Becker Institute of Immunology and InflammationUniversity of ManchesterUK
| | - Shingo Kajimura
- Division of Endocrinology, Diabetes and MetabolismBeth Israel Deaconess Medical Center and Harvard Medical SchoolBostonMAUSA
- Howard Hughes Medical InstituteChevy ChaseMDUSA
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2
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Wang T, Zhou D, Hong Z. Sarcopenia and cachexia: molecular mechanisms and therapeutic interventions. MedComm (Beijing) 2025; 6:e70030. [PMID: 39764565 PMCID: PMC11702502 DOI: 10.1002/mco2.70030] [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: 07/16/2024] [Revised: 11/11/2024] [Accepted: 11/12/2024] [Indexed: 03/17/2025] Open
Abstract
Sarcopenia is defined as a muscle-wasting syndrome that occurs with accelerated aging, while cachexia is a severe wasting syndrome associated with conditions such as cancer and immunodeficiency disorders, which cannot be fully addressed through conventional nutritional supplementation. Sarcopenia can be considered a component of cachexia, with the bidirectional interplay between adipose tissue and skeletal muscle potentially serving as a molecular mechanism for both conditions. However, the underlying mechanisms differ. Recognizing the interplay and distinctions between these disorders is essential for advancing both basic and translational research in this area, enhancing diagnostic accuracy and ultimately achieving effective therapeutic solutions for affected patients. This review discusses the muscle microenvironment's changes contributing to these conditions, recent therapeutic approaches like lifestyle modifications, small molecules, and nutritional interventions, and emerging strategies such as gene editing, stem cell therapy, and gut microbiome modulation. We also address the challenges and opportunities of multimodal interventions, aiming to provide insights into the pathogenesis and molecular mechanisms of sarcopenia and cachexia, ultimately aiding in innovative strategy development and improved treatments.
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Affiliation(s)
- Tiantian Wang
- Department of NeurologyWest China Hospital of Sichuan UniversityChengduSichuanChina
- Institute of Brain Science and Brain‐Inspired Technology of West China HospitalSichuan UniversityChengduSichuanChina
- Department of NeurologyChengdu Shangjin Nanfu HospitalChengduSichuanChina
| | - Dong Zhou
- Department of NeurologyWest China Hospital of Sichuan UniversityChengduSichuanChina
- Institute of Brain Science and Brain‐Inspired Technology of West China HospitalSichuan UniversityChengduSichuanChina
- Department of NeurologyChengdu Shangjin Nanfu HospitalChengduSichuanChina
| | - Zhen Hong
- Department of NeurologyWest China Hospital of Sichuan UniversityChengduSichuanChina
- Institute of Brain Science and Brain‐Inspired Technology of West China HospitalSichuan UniversityChengduSichuanChina
- Department of NeurologyChengdu Shangjin Nanfu HospitalChengduSichuanChina
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3
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Ievleva KD, Danusevich IN, Suturina LV. [The role of leptin in endometrium disorders: literature review]. PROBLEMY ENDOKRINOLOGII 2024; 70:106-114. [PMID: 39509642 DOI: 10.14341/probl13397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 12/19/2023] [Accepted: 12/19/2023] [Indexed: 11/15/2024]
Abstract
Leptin is not only the main regulator of energy balance, but also it affects the reproductive and immune systems. Leptin and its receptors are expressed in the endometrium and are actively involved in the embryo implantation. According to numerous studies, expression and level changes of leptin are associated with the inflammatory and autoimmune diseases, including endometriosis and chronic endometritis. Hyperplastic and inflammatory diseases of the uterus are accompanied by a violation of the receptivity of the endometrium due to the dysregulation of many factors involved in proliferation, vascularization and decidualization of cells. Activity of most of these factors is due to the leptin action, however, there are no studies of the direct effect of leptin in the pathogenesis of disorders of the endometrium in hyperplastic and inflammatory diseases.Thus, the purpose of this literature review was to describe the putative molecular mechanisms of the effect of leptin on the development of endometrial pathology.Literature search was carried out from 03/20/2023 to 05/11/2023 using scientific literature databases: NCBI PubMed, Google Scholar (foreign sources), Cyberleninka, Elibrary (domestic sources): references for the period 1995-2023 were analyzed. The following keywords were used for the search: leptin, endometrial dysfunction, endometrial receptivity, inflammation, pelvic inflammatory disease.
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Affiliation(s)
- K D Ievleva
- Scientific Centre for Family Health and Human Reproduction
| | - I N Danusevich
- Scientific Centre for Family Health and Human Reproduction
| | - L V Suturina
- Scientific Centre for Family Health and Human Reproduction
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Queiroz LGD, Collett-Solberg PF, Souza MDGCD, Rodrigues NCP, Monteiro AM, Mendes CDS, Gazolla FM, Oliveira CLD, Bouskela E, Kuschnir MCC, Madeira IR. Inflammatory markers in prepubertal children and their associations with abdominal fat. J Pediatr (Rio J) 2024; 100:544-551. [PMID: 38734032 PMCID: PMC11361872 DOI: 10.1016/j.jped.2024.03.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 03/25/2024] [Accepted: 03/26/2024] [Indexed: 05/13/2024] Open
Abstract
OBJECTIVE To evaluate the association between inflammatory markers and abdominal fat assessed by ultrasound in prepubertal children with and without excess weight. METHODS A cross-sectional study involving 241 prepubertal children, 156 with obesity, 37 with overweight, and 48 with normal weight, aged five to ten years, who were followed at a research unit on Childhood Obesity from a teaching hospital belonging to a public health system. The concentration of interleukin-6, tumor necrosis factor-α and C-reactive protein were assessed and regression analyses, considering outcome variables such as abdominal wall and intra-abdominal fat thickness measured by ultrasound, were performed. RESULTS The findings highlighted an association between abdominal fat and inflammatory markers, even in children at this young age group. Subcutaneous fat showed a stronger association with inflammatory biomarkers compared to intra-abdominal fat when performing logistic regression, with a positive association between tumor necrosis factor-α and abdominal wall thickness equal to or greater than the 75th percentile in adjusted logistic regression (OR: 18.12; CI 95 %: 1.57: 209.55). CONCLUSIONS Abdominal wall fat, in contrast to what is often observed in adults, appears to have a greater impact on chronic inflammation related to excessive weight in very young children.
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Affiliation(s)
- Letícia G de Queiroz
- Universidade do Estado do Rio de Janeiro, Faculdade de Ciências Médicas, Programa de Pós-Graduação em Ciências Médicas, Rio de Janeiro, RJ, Brazil.
| | - Paulo F Collett-Solberg
- Universidade do Estado do Rio de Janeiro, Faculdade de Ciências Médicas, Departamento de Medicina Interna, Disciplina de Endocrinologia, Rio de Janeiro, RJ, Brazil
| | - Maria das Graças C de Souza
- Universidade do Estado do Rio de Janeiro, Centro Biomédico, Laboratório de Pesquisas Clínicas e Experimentais em Biologia Vascular, Rio de Janeiro, RJ, Brazil
| | - Nádia Cristina P Rodrigues
- Universidade do Estado do Rio de Janeiro, Instituto de Medicina Social Hésio Cordeiro, Rio de Janeiro, RJ, Brazil
| | - Alexandra M Monteiro
- Universidade do Estado do Rio de Janeiro, Faculdade de Ciências Médicas, Rio de Janeiro, RJ, Brazil
| | - Cristiane de S Mendes
- Universidade do Estado do Rio de Janeiro, Hospital Universitário Pedro Ernesto, Laboratório de Hormônios, Rio de Janeiro, RJ, Brazil
| | - Fernanda M Gazolla
- Universidade do Estado do Rio de Janeiro, Hospital Universitário Pedro Ernesto, Unidade de Ensino de Endocrinologia e Metabologia, Rio de Janeiro, RJ, Brazil
| | - Cecília L de Oliveira
- Universidade do Estado do Rio de Janeiro, Instituto de Nutrição, Departamento de Nutrição Aplicada, Rio de Janeiro, RJ, Brazil
| | - Eliete Bouskela
- Universidade do Estado do Rio de Janeiro, Centro Biomédico, Laboratório de Pesquisas Clínicas e Experimentais em Biologia Vascular, Rio de Janeiro, RJ, Brazil
| | - Maria Cristina C Kuschnir
- Universidade do Estado do Rio de Janeiro, Faculdade de Ciências Médicas, Departamento de Pediatria, Rio de Janeiro, RJ, Brazil
| | - Isabel R Madeira
- Universidade do Estado do Rio de Janeiro, Faculdade de Ciências Médicas, Departamento de Pediatria, Rio de Janeiro, RJ, Brazil
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Abdollahi S, Soltani S, Ramezani-Jolfaie N, Mohammadi M, Sherafatmanesh S, Lorzadeh E, Salehi-Abargouei A. The effect of different edible oils on body weight: a systematic review and network meta-analysis of randomized controlled trials. BMC Nutr 2024; 10:107. [PMID: 39080785 PMCID: PMC11290154 DOI: 10.1186/s40795-024-00907-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 07/07/2024] [Indexed: 08/02/2024] Open
Abstract
BACKGROUND Obesity is a major public health issue with no definitive treatment. The first-line approach for obesity is lifestyle modification, including a healthy diet. Although the amount of fat has been considered, there is no network meta-analysis (NMA) study investigating the effect of edible oils on body weight. Therefore, we sought to investigate the effect of different edible oils on body weight using a systematic review and NMA study of randomized controlled trials (RCTs). METHOD PubMed, Scopus, ISI Web of Science, and the Cochrane Library were searched from inception to April 2019. RCTs of different edible oils for body weight were included. A frequentist network meta-analysis was conducted to appraise the efficacy of different types of edible oils, and the Surface Under the Cumulative Ranking Curve (SUCRA) was estimated. The GRADE framework was used to assess the certainty of evidence. RESULTS Forty-two eligible studies were included. Most of the included trials examined the effect of olive oil compared to canola oil (n = 7 studies), followed by canola oil compared to sunflower oil (n = 6 studies), and olive oil compared to sunflower oil (n = 4 studies). Sesame oil had the highest SUCRA value for reducing weight (SUCRA value = 0.9), followed by the mixture of canola and sesame oil (0.8). Palm oil and soy oil were ranked the lowest (SUCRA value = 0.2). CONCLUSION There is low to moderate certainty of evidence showing that soybean, palm, and sunflower oils were associated with weight gain, while sesame oil produced beneficial anti-obesity effects.
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Affiliation(s)
- Shima Abdollahi
- Department of Nutrition, School of Health, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Sepideh Soltani
- Yazd Cardiovascular Research Center, Noncommunicable Diseases Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Nahid Ramezani-Jolfaie
- Food Health Research Center, Hormozgan University of Medical Sci- Ences, Bandar Abbas, Iran
- Department of Community Medicine, School of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Mohammad Mohammadi
- Food Health Research Center, Hormozgan University of Medical Sci- Ences, Bandar Abbas, Iran
- Department of Community Medicine, School of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Saeed Sherafatmanesh
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Research Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Elnaz Lorzadeh
- School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia
| | - Amin Salehi-Abargouei
- Yazd Cardiovascular Research Center, Noncommunicable Diseases Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
- Research Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Scala E, Mercurio L, Albanesi C, Madonna S. The Intersection of the Pathogenic Processes Underlying Psoriasis and the Comorbid Condition of Obesity. Life (Basel) 2024; 14:733. [PMID: 38929716 PMCID: PMC11204971 DOI: 10.3390/life14060733] [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: 04/15/2024] [Revised: 05/20/2024] [Accepted: 06/04/2024] [Indexed: 06/28/2024] Open
Abstract
In the past decade, our understanding of psoriasis pathogenesis has made significant steps forward, leading to the development of multiple game-changing therapies. While psoriasis primarily affects the skin, it is increasingly recognized as a systemic disease that can have effects beyond the skin. Obesity is associated with more severe forms of psoriasis and can potentially worsen the systemic inflammation and metabolic dysfunction seen in psoriatic patients. The exact mechanisms underlying the link between these two conditions are not fully understood, but it is believed that chronic inflammation and immune dysregulation play a role. In this review, we examine the existing body of knowledge regarding the intersection of pathogenic processes responsible for psoriasis and obesity. The ability of biological therapies to reduce systemic and obesity-related inflammation in patients with psoriasis will be also discussed.
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Martínez-Fernández L, Burgos M, Sáinz N, Laiglesia LM, Arbones-Mainar JM, González-Muniesa P, Moreno-Aliaga MJ. Maresin 1 Exerts a Tissue-Specific Regulation of Adipo-Hepato-Myokines in Diet-Induced Obese Mice and Modulates Adipokine Expression in Cultured Human Adipocytes in Basal and Inflammatory Conditions. Biomolecules 2023; 13:919. [PMID: 37371501 DOI: 10.3390/biom13060919] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 05/17/2023] [Accepted: 05/22/2023] [Indexed: 06/29/2023] Open
Abstract
This study analyses the effects of Maresin 1 (MaR1), a docosahexaenoic acid (DHA)-derived specialized proresolving lipid mediator with anti-inflammatory and insulin-sensitizing actions, on the expression of adipokines, including adiponectin, leptin, dipeptidyl peptidase 4 (DPP-4), cardiotrophin-1 (CT-1), and irisin (FNDC5), both in vitro and in in vivo models of obesity. The in vivo effects of MaR1 (50 μg/kg, 10 days, oral gavage) were evaluated in epididymal adipose tissue (eWAT), liver and muscle of diet-induced obese (DIO) mice. Moreover, two models of human differentiated primary adipocytes were incubated with MaR1 (1 and 10 nM, 24 h) or with a combination of tumor necrosis factor-α (TNF-α, 100 ng/mL) and MaR1 (1-200 nM, 24 h) and the expression and secretion of adipokines were measured in both models. MaR1-treated DIO mice exhibited an increased expression of adiponectin and Ct-1 in eWAT, increased expression of Fndc5 and Ct-1 in muscle and a decreased expression of hepatic Dpp-4. In human differentiated adipocytes, MaR1 increased the expression of ADIPONECTIN, LEPTIN, DPP4, CT-1 and FNDC5. Moreover, MaR1 counteracted the downregulation of ADIPONECTIN and the upregulation of DPP-4 and LEPTIN observed in adipocytes treated with TNF-α. Differential effects for TNF-α and MaR1 on the expression of CT-1 and FNDC5 were observed between both models of human adipocytes. In conclusion, MaR1 reverses the expression of specific adipomyokines and hepatokines altered in obese mice in a tissue-dependent manner. Moreover, MaR1 regulates the basal expression of adipokines in human adipocytes and counteracts the alterations of adipokines expression induced by TNF-α in vitro. These actions could contribute to the metabolic benefits of this lipid mediator.
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Affiliation(s)
- Leyre Martínez-Fernández
- Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain
| | - Miguel Burgos
- Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain
- IDISNA-Navarra Institute for Health Research, 31008 Pamplona, Spain
| | - Neira Sáinz
- Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain
| | - Laura M Laiglesia
- Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain
| | - José Miguel Arbones-Mainar
- Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Instituto Aragonés de Ciencias de la Salud (IACS), Instituto de Investigación Sanitaria (IIS) Aragón, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
| | - Pedro González-Muniesa
- Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain
- IDISNA-Navarra Institute for Health Research, 31008 Pamplona, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
| | - María J Moreno-Aliaga
- Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain
- IDISNA-Navarra Institute for Health Research, 31008 Pamplona, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
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Miturski A, Gęca T, Stupak A, Kwaśniewski W, Semczuk-Sikora A. Influence of Pre-Pregnancy Obesity on Carbohydrate and Lipid Metabolism with Selected Adipokines in the Maternal and Fetal Compartment. Nutrients 2023; 15:2130. [PMID: 37432262 DOI: 10.3390/nu15092130] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 04/26/2023] [Accepted: 04/27/2023] [Indexed: 07/12/2023] Open
Abstract
A higher body mass index (BMI) before pregnancy is associated with an increased risk of maternal and perinatal complications. This study aimed to analyze selected parameters of carbohydrate and lipid metabolism, including adipokines, in obese pre-pregnant women, and their influence on the birth weight of newborns. MATERIALS AND METHODS The study group (O) consisted of 34 pregnant women with higher BMI (obese) before pregnancy. The control group (C) was 27 pregnant women with target BMI and physiological pregnancy. The BMI index: body weight [kg]/(height [m]2 was assessed on the first obstetrical visit. The research material was the serum of pregnant women collected in the third trimester of pregnancy and umbilical cord blood collected immediately after delivery. Selected parameters of carbohydrate and lipid metabolism and adipokines were determined. RESULTS There were no statistically significant differences between the study group and the control group concerning the concentrations of insulin, glucose, VLDL, adiponectin, TNF-α, HOMA-IR, as well as LDH and cholesterol in maternal blood serum and umbilical cord blood serum. Total cholesterol and HDL in both maternal blood serum and umbilical cord blood were statistically significantly lower than those in the control group. The concentration of triglycerides (TG) and resistin in the blood serum of obese mothers were higher than those in the control group (p < 0.05). However, no statistically significant differences were found between the two groups regarding the concentrations of TG and resistin in the umbilical cord blood. The concentration of LDL cholesterol in the umbilical blood serum in the obese group was statistically significantly lower than that in the control group. The concentration of leptin in maternal blood serum and umbilical cord blood serum in the study group was statistically significantly higher than that in the control group. CONCLUSIONS Pregestational obesity does not substantially affect the basic parameters of carbohydrate metabolism in pregnant women, but it disturbs the lipid profile, which is manifested by a significant increase in triglycerides and a decrease in the level of HDL cholesterol in the serum. Preexisting obesity increases the concentration of leptin and resistin in the serum of pregnant women, which may be caused by the increased volume of adipose tissue. The concentrations of leptin and resistin in the blood of pregnant women correlate positively, and the concentrations of adiponectin and TNF-α negatively correlate with pre-pregnancy BMI values. There is a positive correlation between the concentration of leptin in the serum of umbilical cord blood and the birth weight of the newborn, which suggests that this parameter contributes to the pathomechanism of macrosomia.
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Affiliation(s)
- Andrzej Miturski
- Department of Gynaecology, 1st Clinical Military Hospital in Lublin, Al. Racławickie 23, 20-049 Lublin, Poland
| | - Tomasz Gęca
- Chair and Department of Obstetrics and Pathology of Pregnancy, Medical University of Lublin, Staszica 16 Street, 20-081 Lublin, Poland
| | - Aleksandra Stupak
- Chair and Department of Obstetrics and Pathology of Pregnancy, Medical University of Lublin, Staszica 16 Street, 20-081 Lublin, Poland
| | - Wojciech Kwaśniewski
- Department of Gynecologic Oncology and Gynecology, Medical University of Lublin, Staszica 16 Street, 20-081 Lublin, Poland
| | - Anna Semczuk-Sikora
- Chair and Department of Obstetrics and Pathology of Pregnancy, Medical University of Lublin, Staszica 16 Street, 20-081 Lublin, Poland
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9
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Wang CJ, Noble PB, Elliot JG, Choi YS, James AL, Wang KCW. Distribution, composition, and activity of airway-associated adipose tissue in the porcine lung. Am J Physiol Lung Cell Mol Physiol 2023; 324:L179-L189. [PMID: 36445102 DOI: 10.1152/ajplung.00288.2022] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Patients with comorbid asthma-obesity experience greater disease severity and are less responsive to therapy. We have previously reported adipose tissue within the airway wall that positively correlated with body mass index. Accumulation of biologically active adipose tissue may result in the local release of adipokines and disrupt large and small airway function depending on its anatomical distribution. This study therefore characterized airway-associated adipose tissue distribution, lipid composition, and adipokine activity in a porcine model. Airway segments were systematically dissected from different locations of the bronchial tree in inflation-fixed lungs. Cryosections were stained with hematoxylin and eosin (H&E) for airway morphology, oil red O to distinguish adipose tissue, and Nile blue A for lipid subtype delineation. Excised airway-associated adipose tissue was cultured for 72 h to quantify adipokine release using immunoassays. Results showed that airway-associated adipose tissue extended throughout the bronchial tree and occupied an area proportionally similar to airway smooth muscle within the wall area. Lipid composition consisted of pure neutral lipids (61.7 ± 3.5%), a mixture of neutral and acidic lipids (36.3 ± 3.4%), or pure acidic lipids (2.0 ± 0.8%). Following tissue culture, there was rapid release of IFN-γ, IL-1β, and TNF-α at 12 h. Maximum IL-4 and IL-10 release was at 24 and 48 h, and peak leptin release occurred between 48 and 72 h. These data extend previous findings and demonstrate that airway-associated adipose tissue is prevalent and biologically active within the bronchial tree, providing a local source of adipokines that may be a contributing factor in airway disease.
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Affiliation(s)
- Carolyn J Wang
- School of Human Sciences, The University of Western Australia, Crawley, Western Australia, Australia
| | - Peter B Noble
- School of Human Sciences, The University of Western Australia, Crawley, Western Australia, Australia
| | - John G Elliot
- School of Human Sciences, The University of Western Australia, Crawley, Western Australia, Australia.,Department of Pulmonary Physiology and Sleep Medicine, West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
| | - Yu Suk Choi
- School of Human Sciences, The University of Western Australia, Crawley, Western Australia, Australia
| | - Alan L James
- Department of Pulmonary Physiology and Sleep Medicine, West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.,Medical School, The University of Western Australia, Nedlands, Western Australia, Australia
| | - Kimberley C W Wang
- School of Human Sciences, The University of Western Australia, Crawley, Western Australia, Australia.,Telethon Kids Institute, The University of Western Australia, Nedlands, Western Australia, Australia
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11
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Aerobic Exercise Prevents Chronic Inflammation and Insulin Resistance in Skeletal Muscle of High-Fat Diet Mice. Nutrients 2022; 14:nu14183730. [PMID: 36145106 PMCID: PMC9503887 DOI: 10.3390/nu14183730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 08/21/2022] [Accepted: 09/06/2022] [Indexed: 11/17/2022] Open
Abstract
Obesity is commonly accompanied by chronic tissue inflammation and leads to insulin resistance. Aerobic exercise is an essential treatment for insulin resistance and has anti-inflammatory effects. However, the molecular mechanisms of exercise on obesity-associated inflammation and insulin resistance remain largely unknown. Here, we evaluated the effects of aerobic exercise on inflammation and insulin resistance in skeletal muscles of high-fat diet (HFD) mice. Male C57BL/6J mice were fed a high-fat diet or a normal diet for 12 weeks, and then aerobic training was performed on a treadmill for 8 weeks. Body weight, fasting blood glucose, food intake levels, and glucose and insulin tolerance were evaluated. The levels of cytokines, skeletal muscle insulin resistance, and inflammation were also analyzed. Eight weeks of aerobic exercise attenuated HFD-induced weight gain and glucose intolerance, and improved insulin sensitivity. This was accompanied by enhanced insulin signaling. Exercise directly resulted in a significant reduction of lipid content, inflammation, and macrophage infiltration in skeletal muscles. Moreover, exercise alleviated HFD-mediated inflammation by suppressing the activation of the NF-κB pathway within skeletal muscles. These results revealed that aerobic exercise could lead to an anti-inflammatory phenotype with protection from skeletal muscle insulin resistance in HFD-induced mice.
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12
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Rogers BM, Stephens JM, Sones JL. Linking Inflammatory Adipose Tissue to Placental Abnormalities in Obese Preeclamptic Pregnancies. Physiol Genomics 2022; 54:319-324. [PMID: 35816649 PMCID: PMC9377783 DOI: 10.1152/physiolgenomics.00041.2022] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Preeclampsia (PE), a pregnancy-specific disorder, is characterized by maternal hypertension and proteinuria or another accompanying sign/symptom of multi-organ dysfunction. Maternal symptoms resolve with delivery of the baby and, importantly, the placenta. Therefore, the placenta plays a causal role in PE. However, the precise cause of abnormal placental development and/or function is unknown. Women with obesity have an increased risk of developing PE that is potentially related to the increased inflammation that accompanies increased maternal adiposity. Furthermore, inflammatory adipokines, i.e., leptin, have been linked to the development of systemic inflammation, hypertension, and other adverse outcomes associated with PE. Rodent models that recapitulate key pathophysiologic features of the maternal and fetal syndrome have been used translationally to study PE. This review covers inflammatory adipokines, immune cells and impaired placental development associated with PE in women and in rodent models of PE that utilize functional genomics to test causation.
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Affiliation(s)
- Brianna M Rogers
- Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, United States.,School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, United States
| | - Jacqueline M Stephens
- Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, United States
| | - Jenny L Sones
- Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, United States.,School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, United States
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13
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Devericks EN, Carson MS, McCullough LE, Coleman MF, Hursting SD. The obesity-breast cancer link: a multidisciplinary perspective. Cancer Metastasis Rev 2022; 41:607-625. [PMID: 35752704 PMCID: PMC9470704 DOI: 10.1007/s10555-022-10043-5] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 05/31/2022] [Indexed: 12/12/2022]
Abstract
Obesity, exceptionally prevalent in the USA, promotes the incidence and progression of numerous cancer types including breast cancer. Complex, interacting metabolic and immune dysregulation marks the development of both breast cancer and obesity. Obesity promotes chronic low-grade inflammation, particularly in white adipose tissue, which drives immune dysfunction marked by increased pro-inflammatory cytokine production, alternative macrophage activation, and reduced T cell function. Breast tissue is predominantly composed of white adipose, and developing breast cancer readily and directly interacts with cells and signals from adipose remodeled by obesity. This review discusses the biological mechanisms through which obesity promotes breast cancer, the role of obesity in breast cancer health disparities, and dietary interventions to mitigate the adverse effects of obesity on breast cancer. We detail the intersection of obesity and breast cancer, with an emphasis on the shared and unique patterns of immune dysregulation in these disease processes. We have highlighted key areas of breast cancer biology exacerbated by obesity, including incidence, progression, and therapeutic response. We posit that interception of obesity-driven breast cancer will require interventions that limit protumor signaling from obese adipose tissue and that consider genetic, structural, and social determinants of the obesity–breast cancer link. Finally, we detail the evidence for various dietary interventions to offset obesity effects in clinical and preclinical studies of breast cancer. In light of the strong associations between obesity and breast cancer and the rising rates of obesity in many parts of the world, the development of effective, safe, well-tolerated, and equitable interventions to limit the burden of obesity on breast cancer are urgently needed.
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Affiliation(s)
- Emily N Devericks
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Meredith S Carson
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Lauren E McCullough
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Michael F Coleman
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Stephen D Hursting
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. .,Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, USA. .,Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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14
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Bazid H, Hammam M, Mostafa M, Gamal Y, El Gayed EMA. Study of leptin gene polymorphism and leptin serum level in alopecia areata patients. J Immunoassay Immunochem 2022; 43:605-617. [PMID: 35726450 DOI: 10.1080/15321819.2022.2088294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Leptin, produced by adipocytes, regulates metabolism, hunger, and immune response. The inflammatory role of leptin has been linked to autoimmune diseases. To assess leptin gene polymorphism and serum level in alopecia areata and their relation to metabolic syndrome (MS). This case-control study was conducted on 100 alopecia areata patients (50 with MS and 50 without MS) and 50 age- and gender-matched controls. Leptin gene polymorphism and serum level were assessed through the use of PCR and ELISA, respectively. GG genotype was the highest in AA with MS (54%), lower in AA without MS (42%), and the lowest in controls (20%). G allele was more expressed in cases, than in controls (P < .001). The serum leptin level was the highest in AA with MS, lower in AA without MS, and the lowest in controls (P value = 0.001). Leptin level was significantly higher in GG polymorphism than AG and AA. Leptin gene polymorphism (GG genotype) and serum level appear to play a significant role in AA. Absent difference regarding leptin gene polymorphism and MS might indicate a separate inflammatory role of leptin or the future risk of MS development in AA patients.
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Affiliation(s)
- Heba Bazid
- Dermatology and Andrology Department, Faculty of Medicine Menoufia University
| | - Mostafa Hammam
- Dermatology and Andrology Department, Faculty of Medicine Menoufia University
| | - Mohammed Mostafa
- Clinical Pathology Department, National Reaserch Center, Cairo, Egypt
| | - Yasmine Gamal
- Dermatology and Andrology Department, Faculty of Medicine Menoufia University
| | - Eman M Abd El Gayed
- Medical Biochemistry and Mollecular biology Department, Faculty of Medicine Menoufia University
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15
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Cordeiro MM, Ribeiro RA, Bubna PB, Almeida AC, Laginski TRF, Franco GCN, Scomparin DX. Physical exercise attenuates obesity development in Western‐diet fed obese rats, independently of vitamin D supplementation. Clin Exp Pharmacol Physiol 2022; 49:633-642. [DOI: 10.1111/1440-1681.13637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 11/12/2021] [Accepted: 11/19/2021] [Indexed: 11/30/2022]
Affiliation(s)
- Maiara Mikuska Cordeiro
- General Biology Department, Biologic Science and Health Sector State University of Ponta Grossa Ponta Grossa Puerto Rico Brazil
| | - Rosane Aparecida Ribeiro
- General Biology Department, Biologic Science and Health Sector State University of Ponta Grossa Ponta Grossa Puerto Rico Brazil
| | - Patrícia Biscaia Bubna
- General Biology Department, Biologic Science and Health Sector State University of Ponta Grossa Ponta Grossa Puerto Rico Brazil
| | - Any Caroline Almeida
- General Biology Department, Biologic Science and Health Sector State University of Ponta Grossa Ponta Grossa Puerto Rico Brazil
| | | | - Gilson César Nobre Franco
- General Biology Department, Biologic Science and Health Sector State University of Ponta Grossa Ponta Grossa Puerto Rico Brazil
| | - Dionízia Xavier Scomparin
- General Biology Department, Biologic Science and Health Sector State University of Ponta Grossa Ponta Grossa Puerto Rico Brazil
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16
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Tiegs G, Horst AK. TNF in the liver: targeting a central player in inflammation. Semin Immunopathol 2022; 44:445-459. [PMID: 35122118 PMCID: PMC9256556 DOI: 10.1007/s00281-022-00910-2] [Citation(s) in RCA: 81] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 01/12/2022] [Indexed: 12/11/2022]
Abstract
Tumour necrosis factor-α (TNF) is a multifunctional cytokine. First recognized as an endogenous soluble factor that induces necrosis of solid tumours, TNF became increasingly important as pro-inflammatory cytokine being involved in the immunopathogenesis of several autoimmune diseases. In the liver, TNF induces numerous biological responses such as hepatocyte apoptosis and necroptosis, liver inflammation and regeneration, and autoimmunity, but also progression to hepatocellular carcinoma. Considering these multiple functions of TNF in the liver, we propose anti-TNF therapies that specifically target TNF signalling at the level of its specific receptors.
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Affiliation(s)
- Gisa Tiegs
- Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. .,Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
| | - Andrea K Horst
- Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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17
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Okubo S, Shindoh J, Kobayashi Y, Umino R, Akabane M, Kojima K, Hashimoto M. Adipose Tissue Distribution Predicts Prognosis of Cirrhotic Patients Undergoing Hepatectomy for Hepatocellular Carcinoma. Ann Surg Oncol 2021; 28:6738-6746. [PMID: 33554286 DOI: 10.1245/s10434-021-09658-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 01/09/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND Body composition data are reportedly correlated with patient prognosis for various cancers. However, little is known about the prognostic impact of adipose tissue distribution among patients with hepatocellular carcinoma (HCC). METHODS Data for 181 consecutive cirrhotic patients who underwent hepatectomy for HCC were retrospectively reviewed. The clinical significance of the visceral-to-subcutaneous adipose tissue ratio (VSR) was investigated through analysis of short- and long-term surgical outcomes. RESULTS Of the 181 patients, 60 (33%) were classified as the high-VSR group and 121 (67%) as the low-VSR group. Although VSR was not correlated with a risk of postoperative morbidity, multivariate analysis confirmed that a higher VSR was significantly correlated with a shorter time to interventional failure (hazard ratio [HR] 2.24; P = 0.008) and overall survival (HR 2.65; P = 0.001) independently of American Joint Committed on Cancer stage or preoperative nutritional status. Analysis of the recurrence patterns showed that the proportion of unresectable recurrence at the initial recurrence event was significantly higher in the high-VSR group (39% vs. 18%; P = 0.025). The yearly transition probabilities, defined by a Markov model from postoperative R0 status to advanced disease or death (7.6% vs. 1.5%, P < 0.001) and early recurrence stage to advanced disease or death (15.4% vs. 2.8%, P = 0.004), were higher in the high-VSR group, suggesting that patients with a higher VSR are vulnerable to disease progression. CONCLUSION A high VSR was found to be an independent predictor of disease progression and poor prognosis for HCC patients with underlying liver cirrhosis having resection for HCC.
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Affiliation(s)
- Satoshi Okubo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Junichi Shindoh
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan.
- Okinaka Memorial Institute for Medical Disease, Tokyo, Japan.
| | - Yuta Kobayashi
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Ryosuke Umino
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Miho Akabane
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Kazutaka Kojima
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Masaji Hashimoto
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
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18
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Pirro F, Caldarola G, Chiricozzi A, Burlando M, Mariani M, Parodi A, Peris K, De Simone C. Impact of Body Mass Index on the Efficacy of Biological Therapies in Patients with Psoriasis: A Real-World Study. Clin Drug Investig 2021; 41:917-925. [PMID: 34537921 PMCID: PMC8481196 DOI: 10.1007/s40261-021-01080-z] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/31/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND The efficacy of biological therapies used for the treatment of chronic plaque psoriasis can be influenced by numerous variables including body mass index (BMI). OBJECTIVE This study aimed to evaluate the impact of BMI on the short-term and long-term efficacy of biological therapies in clinical practice and to identify the best therapeutic options in obese patients (BMI ≥ 30 kg/m2). METHODS A multicentric retrospective study was conducted in patients who initiated a biological therapy during the period January 2006-December 2019. The proportion of patients achieving a 90% improvement of baseline Psoriasis Area and Severity Index at weeks 12 and 24 was calculated also recording the 12- and 24-month drug survival as a measure of long-term efficacy, performing multivariate analyses to assess the impact of different variables. RESULTS Five hundred and four patients with psoriasis were included. After 12 and 24 weeks, the proportion of patients achieving a 90% improvement of baseline Psoriasis Area and Severity Index response was higher in patients with a BMI < 30 kg/m2 compared with those with a BMI ≥ 30 kg/m2 [54.90% vs 43.45% (p = 0.014) at week 12 and 66.84% vs 56.55% (p = 0.021) at week 24]. The Kaplan-Meier survival curves showed how obese patients had a higher probability of discontinuation due to a lack or loss of efficacy (p = 0.0192) compared with non-obese patients. The drug survival analysis also showed that BMI negatively affected the drug survival of secukinumab (odds ratio 1.27, p < 0.001) and ustekinumab (odds ratio 1.06, p = 0.050), while the long-term efficacy of adalimumab, etanercept, and ixekizumab was not influenced by BMI. CONCLUSIONS Obesity (BMI ≥ 30 kg/m2) negatively affects the clinical response of biological drugs in psoriatic patients, with anti-interleukin drugs being more affected by BMI than anti-tumor necrosis factor drugs.
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Affiliation(s)
- Federico Pirro
- Istituto di Dermatologia, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00135, Rome, Italy.
- Department of Dermatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
| | - Giacomo Caldarola
- Istituto di Dermatologia, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00135, Rome, Italy
- Department of Dermatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Andrea Chiricozzi
- Istituto di Dermatologia, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00135, Rome, Italy
- Department of Dermatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Martina Burlando
- Division of Dermatology (DissaL), Policlinico San Martino Hospital, IRCCS, Genoa, Italy
| | - Marco Mariani
- Department of Health Sciences and Public Health, Catholic University, Rome, Italy
| | - Aurora Parodi
- Division of Dermatology (DissaL), Policlinico San Martino Hospital, IRCCS, Genoa, Italy
| | - Ketty Peris
- Istituto di Dermatologia, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00135, Rome, Italy
- Department of Dermatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Clara De Simone
- Istituto di Dermatologia, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00135, Rome, Italy
- Department of Dermatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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19
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Spyrou N, Vallianou N, Kadillari J, Dalamaga M. The interplay of obesity, gut microbiome and diet in the immune check point inhibitors therapy era. Semin Cancer Biol 2021; 73:356-376. [PMID: 33989733 DOI: 10.1016/j.semcancer.2021.05.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 03/22/2021] [Accepted: 05/06/2021] [Indexed: 12/13/2022]
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20
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Costanzo G, Curatolo S, Busà B, Belfiore A, Gullo D. Two birds one stone: semaglutide is highly effective against severe psoriasis in a type 2 diabetic patient. Endocrinol Diabetes Metab Case Rep 2021; 2021:EDM210007. [PMID: 34463640 PMCID: PMC8428016 DOI: 10.1530/edm-21-0007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 07/27/2021] [Indexed: 01/11/2023] Open
Abstract
SUMMARY Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist, approved for the treatment of type 2 diabetes mellitus (T2DM). GLP-1 analogs exert several biological activities connected not only with an insulinotropic effect but also with immunoregulation and reduction of inflammation. A 73-year-old male patient with class III obesity was referred to us for T2DM, which was not controlled with metformin therapy. He had suffered from plaque psoriasis for some years and was treated with topical therapy and adalimumab, without success. The psoriasis area and severity index (PASI) was 33.2 (indicating severe psoriasis), and the dermatology life quality index (DLQI) was 26.0 (indicating an extremely negative effect on the patient's life). Semaglutide (starting with 0.25 mg/week for 4 weeks, increased to 0.50 mg/week for 12 weeks, and then to 1 mg/week) was added to metformin. After 4 months, glycemic parameters had improved, and his body weight decreased. Unexpectedly, skin lesions of plaque psoriasis improved. PASI decreased by 19% compared with baseline and quality of life, assessed with the DLQI, markedly ameliorated. After 10 months, glycemic and obesity parameters, as well as psoriasis, improved further. HbA1c, BMI, and PASI were reduced by 32, 16.3, and 92%, respectively, compared with the baseline. DLQI declined to 0, meaning there was no effect of plaque psoriasis on the patient's life. LEARNING POINTS Psoriasis in patients with type 2 diabetes is often resistant to therapy. We observed an obese patient with type 2 diabetes mellitus who achieved glycemic control and weight loss with the addition of semaglutide to metformin and had a relevant and long-lasting improvement of plaque psoriasis, which was previously resistant to biologic therapy. Therapy with semaglutide may be attempted in eligible patients with difficult to treat plaque psoriasis.
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Affiliation(s)
- Gabriele Costanzo
- Endocrine Unit, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Hospital, Catania, Italy
| | | | - Barbara Busà
- Pharmacy Unit, Garibaldi-Nesima Hospital, Catania, Italy
| | - Antonino Belfiore
- Endocrine Unit, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Hospital, Catania, Italy
| | - Damiano Gullo
- Endocrine Unit, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Hospital, Catania, Italy
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21
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Cordeiro MM, Biscaia PB, Brunoski J, Ribeiro RA, Franco GCN, Scomparin DX. Vitamin D supplementation decreases visceral adiposity and normalizes leptinemia and circulating TNF-α levels in western diet-fed obese rats. Life Sci 2021; 278:119550. [PMID: 33932442 DOI: 10.1016/j.lfs.2021.119550] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 04/12/2021] [Accepted: 04/20/2021] [Indexed: 11/25/2022]
Abstract
AIMS Vitamin (Vit) D regulates various organic processes, including adipose tissue morphofunction and lipid metabolism. Studies indicate that Vit D bioavailability is reduced in obesity, which could contribute to obesity development; however, the effects of Vit D supplementation on increased adiposity in western diet (WD)-obese rats (an experimental model that better resembles the obesogenic human obesity condition) have not been studied, to date. Thus, we hypothesized that Vit D supplementation following the induction of obesity in WD rats might reduce their body weight (BW) and adiposity. MAIN METHODS Male Wistar rats were fed on a standard chow [control (CTL) group] or a WD to induce obesity (WD group), from 21 to 59 days of age. Subsequently, from 60 to 90-days, half of the CTL and of the WD rats were randomly submitted, or not, to oral Vit D supplementation (CTL-VD and WD-VD groups, respectively). KEY FINDINGS At 91 days of age, WD rats were obese, displaying higher abdominal circumference and white fat stores, dyslipidemia, hyperleptinemia and greater plasma levels of tumor necrosis factor (TNF)-α. Vit D supplementation decreased BW gain, abdominal fat deposition and ameliorated the plasma lipid profile in WD-VD rats. These effects were accompanied by reductions in leptinemia and in circulating TNF-α levels in these rodents. SIGNIFICANCE Vit D supplementation, following the induction of obesity, may represent a good strategy to attenuate BW gain and abdominal adiposity, and ameliorate the plasma lipid profile in WD rats. These effects may be mediated, at least in part, by reductions in circulating levels of leptin and TNF-α.
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Affiliation(s)
- Maiara Mikuska Cordeiro
- Departamento de Biologia Geral, Setor de Ciências Biológicas e da Saúde, Universidade Estadual de Ponta Grossa, Ponta Grossa, PR, Brazil
| | - Patrícia Bubna Biscaia
- Departamento de Farmácia, Setor de Ciências Biológicas e da Saúde, Universidade Estadual de Ponta Grossa, Ponta Grossa, PR, Brazil
| | - Janaini Brunoski
- Departamento de Enfermagem e Saúde Pública, Setor de Ciências Biológicas e da Saúde, Universidade Estadual de Ponta Grossa, Ponta Grossa, PR, Brazil
| | - Rosane Aparecida Ribeiro
- Departamento de Biologia Geral, Setor de Ciências Biológicas e da Saúde, Universidade Estadual de Ponta Grossa, Ponta Grossa, PR, Brazil
| | - Gilson César Nobre Franco
- Departamento de Biologia Geral, Setor de Ciências Biológicas e da Saúde, Universidade Estadual de Ponta Grossa, Ponta Grossa, PR, Brazil
| | - Dionizia Xavier Scomparin
- Departamento de Biologia Geral, Setor de Ciências Biológicas e da Saúde, Universidade Estadual de Ponta Grossa, Ponta Grossa, PR, Brazil.
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22
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Al-Rashed F, Sindhu S, Al Madhoun A, Ahmad Z, AlMekhled D, Azim R, Al-Kandari S, Wahid MAA, Al-Mulla F, Ahmad R. Elevated resting heart rate as a predictor of inflammation and cardiovascular risk in healthy obese individuals. Sci Rep 2021; 11:13883. [PMID: 34230580 PMCID: PMC8260607 DOI: 10.1038/s41598-021-93449-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 06/18/2021] [Indexed: 02/06/2023] Open
Abstract
The role of leukocyte inflammatory markers and toll like receptors (TLRs)2/4 in pathologies associated with elevated resting heart rate (RHR) levels in healthy obese (HO) individuals is not well elucidated. Herein, we investigated the relationship of RHR with expression of leukocyte-inflammatory markers and TLRs in HO individuals. 58-obese and 57-lean participants with no history of a major medical condition, were recruited in this study. In HO individuals, the elevated-RHR correlated positively with diastolic blood pressure, cholesterol, pro-inflammatory monocytes CD11b+CD11c+CD206- phenotype (r = 0.52, P = 0.0003) as well as with activated T cells CD8+HLA-DR+ phenotype (r = 0.27, P = 0.039). No association was found between RHR and the percentage of CD16+CD11b+ neutrophils. Interestingly, elevated RHR positively correlated with cells expressing TLR4 and TLR2 (CD14+TLR4+, r = 0.51, P ≤ 0.0001; and CD14+TLR2+, r = 0.42, P = 0.001). TLR4+ expressing cells also associated positively with the plasma concentrations of proinflammatory or vascular permeability/matrix modulatory markers including TNF-α (r = 0.36, P = 0.005), VEGF (r = 0.47, P = 0.0002), and MMP-9 (r = 0.53, P ≤ 0.0001). Multiple regression revealed that RHR is independently associated with CD14+TLR4+ monocytes and VEGF. We conclude that in HO individuals, increased CD14+TLR4+ monocytes and circulatory VEGF levels associated independently with RHR, implying that RHR monitoring could be used as a non-invasive clinical indicator to identify healthy obese individuals at an increased risk of developing inflammation and cardiovascular disease.
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Affiliation(s)
- Fatema Al-Rashed
- Immunology and Microbiology Department, Dasman Diabetes Institute, Al-Soor Street, P.O. Box 1180, 15462, Dasman, Kuwait
| | - Sardar Sindhu
- Animal and Imaging Core Facility, Dasman Diabetes Institute, Dasman, Kuwait
| | - Ashraf Al Madhoun
- Animal and Imaging Core Facility, Dasman Diabetes Institute, Dasman, Kuwait
| | - Zunair Ahmad
- Royal College of Surgeons in Ireland, Busaiteen, Bahrain
| | - Dawood AlMekhled
- School of Biomedical Sciences, Monash University, Melbourne, Australia
| | - Rafaat Azim
- Royal College of Surgeons in Ireland, Busaiteen, Bahrain
| | - Sarah Al-Kandari
- Immunology and Microbiology Department, Dasman Diabetes Institute, Al-Soor Street, P.O. Box 1180, 15462, Dasman, Kuwait
| | | | - Fahd Al-Mulla
- Genetics and Bioinformatics Department, Dasman Diabetes Institute, Dasman, Kuwait
| | - Rasheed Ahmad
- Immunology and Microbiology Department, Dasman Diabetes Institute, Al-Soor Street, P.O. Box 1180, 15462, Dasman, Kuwait.
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23
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Abstract
PURPOSE OF REVIEW From single cells to entire organisms, biological entities are in constant communication with their surroundings, deciding what to 'allow' in, and what to reject. In very different ways, the immune and taste systems both fulfill this function, with growing evidence suggesting a relationship between the two, through shared signaling pathways, receptors, and feedback loops. The purpose of this review was to explore recent reports on taste and immunity in model animals and in humans to explore our understanding of the interplay between these systems. RECENT FINDINGS Acute infections in the upper airway, as with SARS-CoV-2, are associated with a proinflammatory state, and blunted taste perception. Further, recent findings highlight taste receptors working as immune sentinels throughout the body. Work in humans and mice also points to inflammation from obesity impacting taste, altering taste bud abundance and composition. There is accumulating evidence that taste cells, and particularly their receptors, play a role in airway and gut immunity, responsive to invading organisms. Inflammation itself may further act on taste buds and other taste receptor expressing cells throughout the body as a form of homeostatic control.
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Affiliation(s)
- Jason R Goodman
- Department of Food Science, Cornell University, Ithaca, NY, 14853, USA
| | - Robin Dando
- Department of Food Science, Cornell University, Ithaca, NY, 14853, USA.
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24
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The complex role of adipokines in obesity, inflammation, and autoimmunity. Clin Sci (Lond) 2021; 135:731-752. [PMID: 33729498 PMCID: PMC7969664 DOI: 10.1042/cs20200895] [Citation(s) in RCA: 152] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 02/24/2021] [Accepted: 03/04/2021] [Indexed: 12/12/2022]
Abstract
The global obesity epidemic is a major contributor to chronic disease and disability in the world today. Since the discovery of leptin in 1994, a multitude of studies have characterized the pathological changes that occur within adipose tissue in the obese state. One significant change is the dysregulation of adipokine production. Adipokines are an indispensable link between metabolism and optimal immune system function; however, their dysregulation in obesity contributes to chronic low-grade inflammation and disease pathology. Herein, I will highlight current knowledge on adipokine structure and physiological function, and focus on the known roles of these factors in the modulation of the immune response. I will also discuss adipokines in rheumatic and autoimmune diseases.
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25
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Tabatabaie M, Soltani S, Mozaffari-Khosravi H, Salehi-Abargouei A. Zinc Supplementation Might Not Affect Serum Leptin and Adiponectin Levels in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials. IRANIAN JOURNAL OF PUBLIC HEALTH 2021; 50:245-256. [PMID: 33747988 PMCID: PMC7956100 DOI: 10.18502/ijph.v50i2.5337] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Background: Zinc as one of the important trace elements in human health has been suggested to be a supplement for modifying the level of adipokines, whereas findings from studies have been inconsistent. This study aimed to systematically review the evidence provided by randomized controlled trials (RCTs) regarding the effect of zinc supplementation on serum adipokines levels. Methods: PubMed, Google Scholar, Web of Science, and Scopus were systematically searched up to June 2019. The mean differences and their corresponding standard deviations (SDs) of changes in serum adipokines levels were used as effect size. Results: Eight eligible RCTs (leptin n=6, adiponectin n=3) were included in the current study. There were no significant changes in serum leptin levels [weighted mean difference (WMD) =0.60 ng/ml, 95% confidence interval (CI): −1.78, 2.99; I-squared (I2) = 64.3%] and adiponectin levels (WMD = 1.09 ng/ml, 95% CI: −0.76, 3.18, I2 = 78.8%) following zinc supplementation compared to placebo group. These findings did not change after considering several subgroups including gender, study duration, health status, body weight and the type of zinc used for supplementation. Conclusion: No evidence was found to support the efficacy of dietary zinc supplements on serum levels of adipokines. Further, high-quality, long-term controlled clinical trials are warranted to confirm these findings.
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Affiliation(s)
- Mahtab Tabatabaie
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Sepideh Soltani
- Yazd Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Hassan Mozaffari-Khosravi
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Amin Salehi-Abargouei
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Iwabuchi T, Takahashi N, Nishimura T, Rahman MS, Harada T, Okumura A, Kuwabara H, Takagai S, Nomura Y, Matsuzaki H, Ozaki N, Tsuchiya KJ. Associations Among Maternal Metabolic Conditions, Cord Serum Leptin Levels, and Autistic Symptoms in Children. Front Psychiatry 2021; 12:816196. [PMID: 35185642 PMCID: PMC8851349 DOI: 10.3389/fpsyt.2021.816196] [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: 11/16/2021] [Accepted: 12/31/2021] [Indexed: 01/03/2023] Open
Abstract
INTRODUCTION Accumulating evidence has shown that maternal metabolic conditions, such as pre-pregnancy overweight, diabetes mellitus, and hypertensive disorders of pregnancy (HDP) are potential risk factors of autism spectrum disorder (ASD). However, it remains unclear how these maternal conditions lead to neurodevelopmental outcomes in the offspring, including autistic symptoms. Leptin, an adipokine that has pro-inflammatory effects and affects fetal neurodevelopment, is a candidate mediator of the association between maternal metabolic factors and an increased risk of ASD. However, whether prenatal exposure to leptin mediates the association between maternal metabolic conditions and autistic symptoms in children has not been investigated yet. METHODS This study investigated the associations between mothers' metabolic conditions (pre-pregnancy overweight, diabetes mellitus during or before pregnancy, and HDP), leptin concentrations in umbilical cord serum, and autistic symptoms among 762 children from an ongoing cohort study, using generalized structural equation modeling. We used the Social Responsive Scale, Second Edition (SRS-2) at 8-9 years old to calculate total T-scores. Additionally, we used the T-scores for two subdomains: Social Communication and Interaction (SCI) and Restricted Interests and Repetitive Behavior (RRB). RESULTS Umbilical cord leptin levels were associated with pre-pregnancy overweight [coefficient = 1.297, 95% confidence interval (CI) 1.081-1.556, p = 0.005] and diabetes mellitus (coefficient = 1.574, 95% CI 1.206-2.055, p = 0.001). Furthermore, leptin levels were significantly associated with SRS-2 total T-scores (coefficient = 1.002, 95% CI 1.000-1.004, p = 0.023), SCI scores (coefficient = 1.002, 95% CI 1.000-1.004, p = 0.020), and RRB scores (coefficient = 1.001, 95% CI 1.000-1.003, p = 0.044) in children. Associations between maternal metabolic factors and autistic symptoms were not significant. DISCUSSION The present study uncovered an association between cord leptin levels and autistic symptoms in children, while maternal metabolic conditions did not have an evident direct influence on the outcome. These results imply that prenatal pro-inflammatory environments affected by maternal metabolic conditions may contribute to the development of autistic symptoms in children. The findings warrant further investigation into the role of leptin in the development of autistic symptoms.
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Affiliation(s)
- Toshiki Iwabuchi
- Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.,United Graduate School of Child Development, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Nagahide Takahashi
- Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.,United Graduate School of Child Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.,Department of Child and Adolescent Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.,Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tomoko Nishimura
- Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.,United Graduate School of Child Development, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Md Shafiur Rahman
- Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.,United Graduate School of Child Development, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Taeko Harada
- Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.,United Graduate School of Child Development, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Akemi Okumura
- Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.,United Graduate School of Child Development, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Hitoshi Kuwabara
- United Graduate School of Child Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.,Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.,Department of Psychiatry, Saitama Medical University, Saitama, Japan
| | - Shu Takagai
- United Graduate School of Child Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.,Department of Child and Adolescent Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yoko Nomura
- Queens College and Graduate Center, City University of New York, New York City, NY, United States
| | - Hideo Matsuzaki
- Research Center for Child Mental Development, University of Fukui, Fukui, Japan.,United Graduate School of Child Development, University of Fukui, Fukui, Japan
| | - Norio Ozaki
- Department of Child and Adolescent Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.,Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kenji J Tsuchiya
- Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.,United Graduate School of Child Development, Hamamatsu University School of Medicine, Hamamatsu, Japan
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Patel RB, Colangelo LA, Bielinski SJ, Larson NB, Ding J, Allen NB, Michos ED, Shah SJ, Lloyd-Jones DM. Circulating Vascular Cell Adhesion Molecule-1 and Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis (MESA). J Am Heart Assoc 2020; 9:e019390. [PMID: 33161805 PMCID: PMC7763727 DOI: 10.1161/jaha.120.019390] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Background Serum levels of vascular cell adhesion molecule‐1 (VCAM‐1) are reflective of endothelial activation. Although VCAM‐1 has been implicated in the pathogenesis of heart failure with preserved ejection fraction (HFpEF), the prospective association of VCAM‐1 with development of clinically overt heart failure (HF) across ejection fraction categories is unclear. Methods and Results In MESA (the Multi‐Ethnic Study of Atherosclerosis), we evaluated the association of VCAM‐1 at examination 2 (2002–2004) with incident HF (HFpEF and HF with reduced ejection fraction) after adjustment for cardiovascular risk factors. Incident HF was independently adjudicated as first hospitalization for symptomatic HF. Among 2297 participants (mean age, 63 years; women, 53%), those with higher VCAM‐1 were more likely to be White race, had higher blood pressure, and had lower kidney function. Over a median of 14.4 years, there were 102 HF events (HFpEF=65; HF with reduced ejection fraction=37). After covariate adjustment, each doubling of VCAM‐1 was associated with incident HF (hazard ratio [HR], 1.94; 95% CI, 1.17–3.23; P=0.01). This association appeared stronger among current/former smokers compared with never smokers. On evaluation of HF subtypes, VCAM‐1 was associated with incident HFpEF (HR, 1.97; 95% CI, 1.04–3.72; P=0.04) but not with incident HF with reduced ejection fraction, although risk estimates were consistent (HR, 1.82; 95% CI, 0.79–4.21; P=0.16). Conclusions In a multiethnic cohort, VCAM‐1 was significantly associated with incident HF over long‐term follow‐up. These findings suggest a potential role for endothelial activation in driving clinical HF, and specifically HFpEF. Therapies that decrease endothelial activation may prevent the progression from cardiovascular risk factors to clinical HF.
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Affiliation(s)
- Ravi B Patel
- Division of Cardiology Department of Medicine Northwestern University Feinberg School of Medicine Chicago IL.,Department of Preventive Medicine Northwestern University Feinberg School of Medicine Chicago IL
| | - Laura A Colangelo
- Department of Preventive Medicine Northwestern University Feinberg School of Medicine Chicago IL
| | | | | | - Jingzhong Ding
- Department of Internal Medicine Wake Forest School of Medicine Winston-Salem NC
| | - Norrina B Allen
- Department of Preventive Medicine Northwestern University Feinberg School of Medicine Chicago IL
| | - Erin D Michos
- Division of Cardiology Department of Medicine Johns Hopkins University School of Medicine Baltimore MD
| | - Sanjiv J Shah
- Division of Cardiology Department of Medicine Northwestern University Feinberg School of Medicine Chicago IL
| | - Donald M Lloyd-Jones
- Division of Cardiology Department of Medicine Northwestern University Feinberg School of Medicine Chicago IL.,Department of Preventive Medicine Northwestern University Feinberg School of Medicine Chicago IL
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Zhong B, Ma S, Wang DH. Ablation of TRPV1 Elevates Nocturnal Blood Pressure in Western Diet-fed Mice. Curr Hypertens Rev 2020; 15:144-153. [PMID: 30381083 PMCID: PMC6635649 DOI: 10.2174/1573402114666181031141840] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 09/24/2018] [Accepted: 10/24/2018] [Indexed: 12/28/2022]
Abstract
Background: This study tested the hypothesis that genetically ablation of transient receptor potential vanilloid type 1 (TRPV1) exacerbates impairment of baroreflex in mice fed a western diet (WD) and leads to distinct diurnal and nocturnal blood pressure patterns. Methods: TRPV1 gene knockout (TRPV1-/-) and wild-type (WT) mice were given a WD or normal diet (CON) for 4 months. Results: Capsaicin, a selective TRPV1 agonist, increased ipsilateral afferent renal nerve activity in WT but not TRPV1-/- mice. The sensitivity of renal sympathetic nerve activity and heart rate responses to baroreflex were reduced in TRPV1-/--CON and WT-WD and further decreased in TRPV1-/--WD compared to the WT-CON group. Urinary norepinephrine and serum insulin and leptin at day and night were increased in WT-WD and TRPV1-/--WD, with further elevation at night in TRPV1-/--WD. WD intake increased leptin, IL-6, and TNF-α in adipose tissue, and TNF-α antagonist III, R-7050, decreased leptin in TRPV1-/--WD. The urinary albumin level was higher in TRPV1-/--WD than WT-WD. Blood pressure was not dif-ferent during daytime among all groups, but increased at night in the TRPV1-/--WD group compared with other groups. Conclusions: TRPV1 ablation leads to elevated nocturnal but not diurnal blood pressure, which is probably attributed to fur-ther enhancement of sympathetic drives at night.
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Affiliation(s)
- Beihua Zhong
- Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, East Lansing, Michigan MI 48824, United States
| | - Shuangtao Ma
- Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, East Lansing, Michigan MI 48824, United States
| | - Donna H Wang
- Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, East Lansing, Michigan MI 48824, United States.,Neuroscience Program, Michigan State University, East Lansing, Michigan MI 48824, United States.,Cell & Molecular Biology Program, Michigan State University, East Lansing, Michigan MI 48824, United States
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29
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Tobore TO. Towards a comprehensive theory of obesity and a healthy diet: The causal role of oxidative stress in food addiction and obesity. Behav Brain Res 2020; 384:112560. [DOI: 10.1016/j.bbr.2020.112560] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 02/14/2020] [Accepted: 02/14/2020] [Indexed: 02/06/2023]
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Ramanathan K, Padmanabhan G. Soluble neprilysin: A versatile biomarker for heart failure, cardiovascular diseases and diabetic complications-A systematic review. Indian Heart J 2020; 72:14-19. [PMID: 32423555 PMCID: PMC7231860 DOI: 10.1016/j.ihj.2020.01.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 12/09/2019] [Accepted: 01/27/2020] [Indexed: 12/11/2022] Open
Abstract
The potential role of soluble neprilysin (sNEP) as a biomarker has been poorly documented. Hence, the present systematic review emphasizes to explore sNEP as an emerging biomarker for heart failure (HF), cardiovascular diseases, diabetic kidney diseases, and so on. A systematic review was performed using an online database search in PubMed, Science Direct, Scopus, and Cochrane Library. Articles reporting biomarker's performance to diagnose various diseases in human participants were included. The results of the search outcome were 4723 articles. Based on the inclusion criteria of the systematic review, finally, 12 articles fulfilled the selection criteria. In these studies, 8 cohort study, 2 cross-sectional study, 1 case-control, and 1 prospective cohort study were identified. All these studies clearly suggested sNEP as a potential biomarker for diagnosis of various diseases (HF, cardiovascular diseases, diabetic kidney diseases, metabolic syndrome). sNEP may be a potential biomarker for HF, cardiovascular diseases, diabetic kidney disease, and so on.
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Affiliation(s)
- Kumaresan Ramanathan
- Department of Medical Biochemistry, Division of Biomedical Sciences, School of Medicine, College of Health Sciences, Mekelle University (Ayder Campus), Mekelle, Ethiopia.
| | - Giri Padmanabhan
- Kidney Care, C50,10th B Cross, Thillai Nagar, Tiruchirappalli, India.
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31
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Cruz MM, Simão JJ, de Sá RDCC, Farias TSM, da Silva VS, Abdala F, Antraco VJ, Armelin-Correa L, Alonso-Vale MIC. Palmitoleic Acid Decreases Non-alcoholic Hepatic Steatosis and Increases Lipogenesis and Fatty Acid Oxidation in Adipose Tissue From Obese Mice. Front Endocrinol (Lausanne) 2020; 11:537061. [PMID: 33117273 PMCID: PMC7561405 DOI: 10.3389/fendo.2020.537061] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Accepted: 08/28/2020] [Indexed: 01/06/2023] Open
Abstract
We recently demonstrated that palmitoleic acid (C16:1n7), a monounsaturated fatty acid, increases the metabolic and oxidative capacity of 3T3-L1 adipocytes. Herein, the effect of 16:1n7 supplementation on metabolic parameters on white adipose tissue (WAT) and liver of obese mice induced by a high-fat diet (HFD) was addressed by analyzing metabolic (dys)function and altered genes expression in adipose tissue, as well as liver and serum biochemistry analysis. For this purpose, mice were induced to obesity for 8 weeks, and from the 5th week, they received 16:1n7 (300 mg/kg per day) or water for 30 days, by gavage. Subcutaneous inguinal (ING) and epididymal (EPI) WAT were removed for analysis of metabolic, (anti)inflammatory, adipogenic, and thermogenic genes expression by real-time reverse transcriptase-polymerase chain reaction. Additionally, metabolic activities of isolated adipocytes, such as glucose uptake, lipogenesis (triacylglycerol esterification), β-oxidation, and lipolysis in ING adipocytes, were also assessed. Despite the higher fat intake, the HFD group showed lower food intake but higher body weight, increased glucose, significant dyslipidemia, and increased liver and adipose depot mass, accompanied by liver steatosis. The 16:1n7 supplementation slowed down the body mass gain and prevented the increase of lipids in the liver. HFD+n7 animals presented increased fatty acid oxidation and lipogenesis compared to control, but no effect was observed on lipolysis and glucose uptake in ING isolated adipocytes. Besides, 16:1n7 increased the content of the mRNA encoding FABP4, but partially prevented the expression of genes encoding ATGL, HSL, perilipin, lipin, C/EBP-α, PPAR-γ, C/EBP-β, CPT1, NRF1, TFAM, PRDM16, and nitric oxide synthase 2 in ING depot from HFD group of animals. Finally, HFD increased Mcp1 and Tnfα expression, and 16:1n7 promoted a more marked increase in it. In summary, the data show that palmitoleic acid promotes metabolic changes and partially prevents the increase in gene expression on adipocytes triggered by obesity, suggesting that HFD+n7 animals do not require the same magnitude of metabolic adaptation to cope with energy demand from the HFD. In the long term, the effects of 16:1n7 may be more evident and beneficial for the function/dysfunction of WAT from an obese organism, with relevant repercussions in the systemic metabolic homeostasis.
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Affiliation(s)
- Maysa M. Cruz
- Post-graduate Program in Chemical Biology – Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
| | - Jussara J. Simão
- Post-graduate Program in Chemical Biology – Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
| | - Roberta D. C. C. de Sá
- Post-graduate Program in Chemical Biology – Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
| | - Talita S. M. Farias
- Post-graduate Program in Chemical Biology – Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
| | - Viviane S. da Silva
- Post-graduate Program in Chemical Biology – Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
| | - Fernanda Abdala
- Department of Biological Sciences, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
| | - Vitor J. Antraco
- Post-graduate Program in Chemical Biology – Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
| | - Lucia Armelin-Correa
- Post-graduate Program in Chemical Biology – Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
- Department of Biological Sciences, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
| | - Maria Isabel C. Alonso-Vale
- Post-graduate Program in Chemical Biology – Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
- Department of Biological Sciences, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
- *Correspondence: Maria Isabel C. Alonso-Vale
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The Influence of Photoperiod on the Action of Exogenous Leptin on Gene Expression of Proinflammatory Cytokines and Their Receptors in the Thoracic Perivascular Adipose Tissue (PVAT) in Ewes. Mediators Inflamm 2019; 2019:7129476. [PMID: 31780867 PMCID: PMC6875191 DOI: 10.1155/2019/7129476] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Revised: 09/02/2019] [Accepted: 10/09/2019] [Indexed: 12/31/2022] Open
Abstract
Leptin resistance is either a condition induced by human obesity or a natural phenomenon associated with seasonality in ruminants. In the cardiovascular system, the leptin resistance state presence is a complex issue. Moreover, the perivascular adipose tissue (PVAT) appears to be crucial as a source of proinflammatory cytokines and as a site of interaction for leptin contributing to endothelium dysfunction and atherosclerosis progression. So the aim of this study was to examine the influence of the photoperiod on the action of exogenous leptin on gene expression of selected proinflammatory cytokines and their receptors in thoracic PVAT of ewe with or without prior lipopolysaccharide (LPS) stimulation. The experiment was conducted on 48 adult, female ewes divided into 4 group (n = 6 in each): control, with LPS intravenous (iv.) injection (400 ng/kg of BW), with leptin iv. injection (20 μg/kg BW), and with LPS and 30-minute-later leptin injection, during short-day (SD) and long-day (LD) seasons. Three hours after LPS/control treatment, animals were euthanized to collect the PVAT adherent to the aorta wall. The leptin injection enhanced IL1B gene expression only in the LD season; however, in both seasons leptin injection intensified LPS-induced increase in IL1B gene expression. IL1R2 gene expression was increased by leptin injection only in the SD season. Neither IL6 nor its receptor and signal transducer gene expressions were influenced by leptin administration. Leptin injection increased TNFA gene expression regardless of photoperiodic conditions. Only in the SD season did leptin treatment increase the gene expression of both TNFα receptors. To conclude, leptin may modulate the inflammatory reaction progress in PVAT. In ewe, the sensitivity of PVAT on leptin action is dependent upon the photoperiodic condition with stronger effects stated in the SD season.
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Chiricozzi A, Gisondi P, Girolomoni G. The pharmacological management of patients with comorbid psoriasis and obesity. Expert Opin Pharmacother 2019; 20:863-872. [DOI: 10.1080/14656566.2019.1583207] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Affiliation(s)
- Andrea Chiricozzi
- Institute of Dermatology, Catholic University - Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Paolo Gisondi
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy
| | - Giampiero Girolomoni
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy
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34
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Kim J, Jung E, Choi J, Min DY, Lee YH, Shin SY. Leptin is a direct transcriptional target of EGR1 in human breast cancer cells. Mol Biol Rep 2018; 46:317-324. [PMID: 30417207 DOI: 10.1007/s11033-018-4474-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Accepted: 11/07/2018] [Indexed: 12/13/2022]
Abstract
Leptin is a cytokine that regulates energy metabolism. Leptin can promote breast cancer progression in obese women. However, the mechanism of regulation of leptin expression in breast cancer cells is unclear. Tumor necrosis factor-alpha (TNF-α) stimulated the transcription of the leptin gene. Using mutant promoter constructs, we demonstrated that the EGR1-binding motif in the proximal region of the leptin gene is required for leptin transcription by TNF-α. Forced expression of EGR1 stimulated leptin promoter activity, whereas silencing of EGR1 by RNA interference reduced TNF-α-induced leptin protein accumulation. The ERK1/2 pathway contributed to the expression of EGR1 and leptin by TNF-α. Our results suggest that EGR1 targets the leptin gene in response to TNF-α stimulation in breast cancer cells.
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Affiliation(s)
- JuHwan Kim
- Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University, Seoul, 05029, Republic of Korea
| | - Euitaek Jung
- Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University, Seoul, 05029, Republic of Korea
| | - Jihye Choi
- Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University, Seoul, 05029, Republic of Korea
| | - Dong Yeong Min
- Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University, Seoul, 05029, Republic of Korea
| | - Young Han Lee
- Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University, Seoul, 05029, Republic of Korea.,Cancer and Metabolism Institute, Konkuk University, Seoul, 05029, Republic of Korea
| | - Soon Young Shin
- Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University, Seoul, 05029, Republic of Korea. .,Cancer and Metabolism Institute, Konkuk University, Seoul, 05029, Republic of Korea.
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35
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Yang TY, Gardner JC, Gentile JD, Liang NC. Sex and individual differences in meal patterns mediate the persistency of running-associated high-fat diet avoidance in rats. Am J Physiol Regul Integr Comp Physiol 2018; 316:R130-R143. [PMID: 30403499 DOI: 10.1152/ajpregu.00231.2018] [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] [Indexed: 12/26/2022]
Abstract
The modern environment is characterized by convenient access to a variety of high-fat (HF) foods and encourages excess energy intake, which leads to weight gain. While healthier diets and exercise are common interventions that facilitate energy balance, meal patterns also influence body weight and energy metabolism. The current study characterized the association among exercise, diet choice, and meal patterns in rats. Unlike sedentary rats, which prefer a HF to a chow diet, wheel-running rats initially avoid the HF diet. Subsequently, the running-induced HF diet avoidance persists longer in males than in females. We hypothesized that differences in meal patterns contribute to sex differences in the prevalence and persistency of HF diet avoidance. During two-diet choice, rats did not mix chow and HF diet within a meal and consumed discrete meals of each diet. Exercise decreased chow meal size in both sexes (4.5 vs. 5.7 kcal) but decreased total meal frequency only in male rats. Analyses of individual differences revealed WR rats that maintained HF diet avoidance (HF avoiders) had larger chow than HF meals (5.2 vs. 1.3 kcal) upon initial 3 days of diet choice. When compared with rats that reversed HF avoidance (HF eaters), HF avoiders had shorter latency to consume their first meal of HF diet (2.6 vs. 98.9 min) upon initial running and diet choice. Taken together, these results suggest that both sex and individual differences in meal patterns contribute to differences in the persistency of exercise-associated HF diet avoidance.
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Affiliation(s)
- Tiffany Y Yang
- Department of Psychology, University of Illinois at Urbana-Champaign , Champaign, Illinois
| | - Jennie C Gardner
- Department of Psychology, University of Illinois at Urbana-Champaign , Champaign, Illinois
| | | | - Nu-Chu Liang
- Department of Psychology, University of Illinois at Urbana-Champaign , Champaign, Illinois.,Neuroscience Program, University of Illinois at Urbana-Champaign , Urbana, Illinois.,Division of Nutritional Sciences, University of Illinois at Urbana-Champaign , Urbana, Illinois
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36
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Pro-inflammatory cytokines: The link between obesity and osteoarthritis. Cytokine Growth Factor Rev 2018; 44:38-50. [PMID: 30340925 DOI: 10.1016/j.cytogfr.2018.10.002] [Citation(s) in RCA: 605] [Impact Index Per Article: 86.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Revised: 10/06/2018] [Accepted: 10/08/2018] [Indexed: 02/05/2023]
Abstract
Osteoarthritis (OA), characterized by joint malfunction and chronic disability, is the most common form of arthritis. Clinical and animal experiments reveal that age-related OA is associated with many factors such as age, sex, trauma, and obesity. One of the most influential and modifiable risk factors is obesity. Obesity not only increases mechanical stress on the tibiofemoral cartilage, but also leads to a higher prevalence of OA in non-weight-bearing areas. There is a link between obesity and inflammation. Adipose tissues play a crucial role in this context because they are the major source of cytokines, chemokines, and metabolically-active mediators named adipokines. The adipokines, including adiponectin and leptin, have been demonstrated to regulate inflammatory immune responses in cartilage. Obese people and animals show a higher level of serum tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL)-1β and IL-6, all of which are produced by macrophages derived from adipose tissue. These pro-inflammatory cytokines regulate the proliferation and apoptosis of adipocytes, promote lipolysis, inhibit lipid synthesis and decrease blood lipids through autocrine and paracrine mechanisms. Elevated levels of TNF-α, IL-1 and IL-6 have been found in the synovial fluid, synovial membrane, subchondral bone and cartilage of OA patients, confirming their important roles in OA pathogenesis. TNF-α, IL-6 and IL-1 are the factors released by fat to negatively regulate cartilage directly. Moreover, TNF-α, IL-1 and IL-6 can induce the production of other cytokines, matrix metalloproteinases (MMPs) and prostaglandins and inhibit the synthesis of proteoglycans and type II collagen; thus, they play a pivotal role in cartilage matrix degradation and bone resorption in OA. Activated chondrocytes also produce MMP-1, MMP-3, MMP-13, and aggrecanase 1 and 2 (ADAMTS-4, ADAMTS-5). In addition, IL-1, TNF-α and IL-6 may cause OA indirectly by regulating release of adiponectin and leptin from adipocytes. In this review, we first summarize the relationship between obesity and inflammation. Then we summarize the roles of IL-1, TNF-α and IL-6 in OA. We further discuss how IL-1, TNF-α and IL-6 regulate the communication between fat and OA, and their pathological roles in obesity-related OA. Lastly, we discuss the possibility of using the pro-inflammatory signaling pathway as a therapeutic target to develop drugs for obesity-related OA.
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Donnelly JM, Lindsay K, Walsh JM, Horan MK, O'Shea D, Molloy EJ, McAuliffe FM. Perinatal inflammation and childhood adiposity - a gender effect? J Matern Fetal Neonatal Med 2018; 33:1203-1210. [PMID: 30261783 DOI: 10.1080/14767058.2018.1517315] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Background: To determine the association of maternal and fetal inflammatory factors with gender-specific infant adiposity, independent of leptin.Methods: Analysis of anthropometry from 265 mother-infant pairs at birth and 280 pairs at 6 months from the randomised control trial of low glycaemic index diet in pregnancy (ROLO) study (Randomised control trial of low glycaemic index diet) and their association with Maternal TNF-alpha, interleukin 6 and leptin as measured in early and late pregnancy and fetal levels in cord blood.Results: No associations were noted in the male cohort. On multiple regression amongst the female neonatal cohort late pregnancy IL-6 was inversely associated with sum of skinfolds (p ≤ .001); at 6 months infant sum of skinfolds were positively associated with early pregnancy IL-6 (p = .046) and central adiposity positively associated with early pregnancy TNF alpha (p = .018) independent of leptin.Conclusion: Although maternal inflammatory cytokines were not associated with neonatal adiposity independent of leptin (as this association is known), both IL-6 and TNF-α were associated with female infant anthropometry at 6 months of age independent of leptin. These results suggest inflammatory cytokines may exert an in-utero influence on later infant adiposity with a tendency to influence female adiposity more than male. Further research is required to ascertain whether these cytokines may be used as reliable early predictors of infant adiposity.
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Affiliation(s)
- Jean M Donnelly
- UCD Obstetrics and Gynecology, School of Medicine and Medical Science, University College Dublin, National Maternity Hospital, Dublin, Ireland
| | - Karen Lindsay
- UCD Obstetrics and Gynecology, School of Medicine and Medical Science, University College Dublin, National Maternity Hospital, Dublin, Ireland
| | - Jennifer M Walsh
- UCD Obstetrics and Gynecology, School of Medicine and Medical Science, University College Dublin, National Maternity Hospital, Dublin, Ireland
| | - Mary K Horan
- UCD Obstetrics and Gynecology, School of Medicine and Medical Science, University College Dublin, National Maternity Hospital, Dublin, Ireland
| | - Donal O'Shea
- School of Medicine and Medical Science, St. Vincent's Hospital, Dublin, Ireland
| | - Eleanor J Molloy
- Department of Paediatrics, University of Dublin, Dublin, Ireland.,Department of Neonatology, Our Lady's Children's Hospital, Crumlin, Ireland.,Department of Neonatology, Coombe Women and Infants Hospital, Dublin, Ireland
| | - Fionnuala M McAuliffe
- UCD Obstetrics and Gynecology, School of Medicine and Medical Science, University College Dublin, National Maternity Hospital, Dublin, Ireland
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38
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Canter RJ, Le CT, Beerthuijzen JM, Murphy WJ. Obesity as an immune-modifying factor in cancer immunotherapy. J Leukoc Biol 2018; 104:487-497. [PMID: 29762866 PMCID: PMC6113103 DOI: 10.1002/jlb.5ri1017-401rr] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Revised: 04/17/2018] [Accepted: 04/18/2018] [Indexed: 12/18/2022] Open
Abstract
Immunotherapy has achieved breakthrough status in many advanced stage malignancies and is rapidly becoming the fourth arm of cancer treatment. Although cancer immunotherapy has generated significant excitement because of the potential for complete and sometimes durable responses, there is also the potential for severe and occasionally life-threatening toxicities, including cytokine release syndrome and severe autoimmunity. A large body of work also points to a "metainflammatory" state in obesity associated with impairment of immune responses. Because immune checkpoint blockade (and other cancer immunotherapies) have altered the landscape of immunotherapy in cancer, it is important to understand how immune responses are shaped by obesity and how obesity may modify both immunotherapy responses and potential toxicities.
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Affiliation(s)
- Robert J. Canter
- University of California, Davis, School of Medicine, Department of Surgery, Division of Surgical Oncology, Sacramento, CA 95817
| | - Catherine T Le
- University of California, Davis, School of Medicine, Departments of Dermatology and Internal Medicine, Sacramento, CA 95817
| | - Johanna M.T. Beerthuijzen
- University of California, Davis, School of Medicine, Departments of Dermatology and Internal Medicine, Sacramento, CA 95817
| | - William J. Murphy
- University of California, Davis, School of Medicine, Departments of Dermatology and Internal Medicine, Sacramento, CA 95817
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Impact of obesity on autoimmune arthritis and its cardiovascular complications. Autoimmun Rev 2018; 17:821-835. [PMID: 29885537 PMCID: PMC9996646 DOI: 10.1016/j.autrev.2018.02.007] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Accepted: 02/25/2018] [Indexed: 02/06/2023]
Abstract
Obesity can instigate and sustain a systemic low-grade inflammatory environment that can amplify autoimmune disorders and their associated comorbidities. Metabolic changes and inflammatory factors produced by the adipose tissue have been reported to aggravate autoimmunity and predispose the patient to cardiovascular disease (CVD) and metabolic comorbidities. Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are autoimmune arthritic diseases, often linked with altered body mass index (BMI). Severe joint inflammation and bone destruction have a debilitating impact on the patient's life; there is also a staggering risk of cardiovascular morbidity and mortality. Furthermore, these patients are at risk of developing metabolic symptoms, including insulin resistance resulting in type 2 diabetes mellitus (T2DM). In addition, arthritis severity, progression and response to therapy can be markedly affected by the patient's BMI. Hence, a complex integrative pathogenesis interconnects autoimmunity with metabolic and cardiovascular disorders. This review aims to shed light on the network that connects obesity with RA, PsA, systemic lupus erythematosus and Sjӧgren's syndrome. We have focused on clarifying the mechanism by which obesity affects different cell types, inflammatory factors and traditional therapies in these autoimmune disorders. We conclude that to further optimize arthritis therapy and to prevent CVD, it is imperative to uncover the intricate relation between obesity and arthritis pathology.
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Dalton B, Bartholdy S, Robinson L, Solmi M, Ibrahim MAA, Breen G, Schmidt U, Himmerich H. A meta-analysis of cytokine concentrations in eating disorders. J Psychiatr Res 2018; 103:252-264. [PMID: 29906710 DOI: 10.1016/j.jpsychires.2018.06.002] [Citation(s) in RCA: 119] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Revised: 05/16/2018] [Accepted: 06/01/2018] [Indexed: 01/02/2023]
Abstract
Cytokines are signalling molecules, which play an important role in both immune system function and brain development and function, and subsequently mental states and behaviour. Cytokines have been implicated in eating disorders (EDs) due to their role in psychological health, body weight and appetite regulation. This meta-analysis examined cross-sectional and longitudinal studies measuring concentrations of cytokines in individuals with EDs. Using PRISMA guidelines, we systematically reviewed relevant articles in PubMed, Web of Science, and MEDLINE. Random-effects meta-analyses were conducted for interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β, and tumor necrosis factor (TNF)-α, independently, firstly with all EDs combined and then stratified by ED diagnosis. Twenty-five studies were included: serum/plasma cytokine concentrations were measured in people with anorexia nervosa (AN) in 23 studies and bulimia nervosa (BN) in 4 studies. TNF-α and IL-6 were elevated in ED participants compared to healthy controls (HCs). Specifically, this pattern was seen only when comparing AN participants to HCs. Concentrations of these cytokines did not differ between people with BN and HCs. IL-1β and TGF-β did not differ between HCs and any ED group. Therefore, AN seems to be associated with elevated concentrations of TNF-α and IL-6. Considering the role of cytokines in appetite, mood regulation, and anxiety, these pro-inflammatory cytokines could be a potential future drug target to help people with AN, not only with weight gain, but also with various coexisting psychological problems. Future studies should consider confounding factors that affect cytokine concentrations and report ED-relevant clinical characteristics.
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Affiliation(s)
- Bethan Dalton
- Section of Eating Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK.
| | - Savani Bartholdy
- Section of Eating Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK
| | - Lauren Robinson
- Section of Eating Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK
| | - Marco Solmi
- Department of Neurosciences, Psychiatry Unit, University of Padua, Padua, Italy; Cognitive Neuroscience Center, University of Padua, Padua, Italy; University Hospital Padua, Padua, Italy
| | - Mohammad A A Ibrahim
- Department of Immunological Medicine and Allergy, King's Health Partners, King's College Hospital, London SE5 9RS, UK
| | - Gerome Breen
- MRC Social, Genetic, and Developmental Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK
| | - Ulrike Schmidt
- Section of Eating Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK; South London and Maudsley NHS Foundation Trust, London, UK
| | - Hubertus Himmerich
- Section of Eating Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK; South London and Maudsley NHS Foundation Trust, London, UK
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41
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Ali Z, Suppli Ulrik C, Agner T, Thomsen SF. Is atopic dermatitis associated with obesity? A systematic review of observational studies. J Eur Acad Dermatol Venereol 2018; 32:1246-1255. [PMID: 29444366 DOI: 10.1111/jdv.14879] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Accepted: 01/25/2018] [Indexed: 12/06/2024]
Abstract
Obesity has been associated with atopic dermatitis (AD); however, the results have been conflicting. Our aim was to provide an update on current knowledge from observational studies addressing the possible association between obesity and AD. Systematic literature review was performed by identifying studies addressing a possible link between AD and overweight/obesity from PubMed, EMBASE and the Cochrane Library in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. A total of 45 studies (comprising more than 90 000 individuals with AD) fulfilled the criteria and were included in the present review. The available studies revealed inconsistencies, but the majority indicated that obesity is associated with AD. Studies addressing obesity in infancy or early childhood (age < 2 years) and AD reported a positive association. From childhood into adulthood, there is a discrepancy in the observations, as the more recent prospective studies found a positive association, whereas this was not observed in older cross-sectional studies. The inconsistency might be explained by the difference in study design, the diagnostic criteria of AD, regional differences, and by the varied definitions of overweight and obesity used in the studies. In Conclusion, overweight/obesity is associated with an increased risk of AD. Large prospective cohort studies are required to confirm the association between AD and obesity and the possibility that weight control in childhood may help to mitigate or reverse AD symptoms.
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Affiliation(s)
- Z Ali
- Department of Pulmonary Medicine, Hvidovre Hospital, Hvidovre, Denmark
- Department of Dermatology, Bispebjerg Hospital, Copenhagen NV, Denmark
| | - C Suppli Ulrik
- Department of Pulmonary Medicine, Hvidovre Hospital, Hvidovre, Denmark
- Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - T Agner
- Department of Dermatology, Bispebjerg Hospital, Copenhagen NV, Denmark
| | - S F Thomsen
- Department of Dermatology, Bispebjerg Hospital, Copenhagen NV, Denmark
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
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Carreras NL, Martorell P, Chenoll E, Genovés S, Ramón D, Aleixandre A. Anti-obesity properties of the strain Bifidobacterium animalis subsp. lactis CECT 8145 in Zücker fatty rats. Benef Microbes 2018; 9:629-641. [DOI: 10.3920/bm2017.0141] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
We evaluated the effect of oral administration of Bifidobacterium animalis subsp. lactis CECT 8145 strain in Zücker fatty rats. The Zücker fatty rats were randomly divided into two groups (n=10 each) and administered either B. animalis subsp. lactis CECT 8145 (1010 cfu/day) suspended in skim milk, or skim milk alone (control group). Each treatment was administered in drinking bottles from week 5 until week 17 of age. A lean Zücker rat group (standard group) was included to provide normal values for the Zücker strain. This group was administered skim milk in the drinking bottle for the same experimental period as Zücker fatty rats. Body weight gain was greater in the fatty control group than in the fatty rats treated daily with B. animalis subsp. lactis CECT 8145. Furthermore, dry and liquid food intake significantly decreased in the treated Zücker fatty group and these rats also showed decreased plasma ghrelin levels as compared with the Zücker fatty control group. B. animalis subsp. lactis CECT 8145 intake also decreased plasma tumour necrosis factor-α (a proinflammatory cytokine) and plasma malondialdehyde (a biomarker of oxidative stress). Moreover, the ratio plasma total cholesterol/plasma cholesterol transported by high-density lipoproteins, considered as an index for cardiovascular disease, also significantly decreased in the Zücker fatty rats treated with B. animalis subsp. lactis CECT 8145. By contrast, this bacterial strain significantly increased plasma adiponectin (an insulin-sensitising adipokine), but did not produce significant effects on triglyceride levels or glucose metabolism biomarkers. Although further research is required to confirm B. animalis subsp. lactis CECT 8145 is an efficient anti-obesity treatment in humans, the results obtained in this study are promising and point to the health and anti-obesity properties of this bacterial strain.
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Affiliation(s)
- N. López Carreras
- Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, Avenida Complutense s/n, 28040 Madrid, Spain
| | - P. Martorell
- Department of Food Biotechnology; Biópolis S.L. Parc Científic Universitat De València, Edif. 2, C/Catedrático Agustín Escardino Benlloch, 9, 46980 Paterna, Spain
| | - E. Chenoll
- Department of Food Biotechnology; Biópolis S.L. Parc Científic Universitat De València, Edif. 2, C/Catedrático Agustín Escardino Benlloch, 9, 46980 Paterna, Spain
| | - S. Genovés
- Department of Food Biotechnology; Biópolis S.L. Parc Científic Universitat De València, Edif. 2, C/Catedrático Agustín Escardino Benlloch, 9, 46980 Paterna, Spain
| | - D. Ramón
- Department of Food Biotechnology; Biópolis S.L. Parc Científic Universitat De València, Edif. 2, C/Catedrático Agustín Escardino Benlloch, 9, 46980 Paterna, Spain
| | - A. Aleixandre
- Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, Avenida Complutense s/n, 28040 Madrid, Spain
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43
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Affiliation(s)
- Milton Packer
- Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX
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44
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Targeted disruption of the iNOS gene improves adipose tissue inflammation and fibrosis in leptin-deficient ob/ob mice: role of tenascin C. Int J Obes (Lond) 2018; 42:1458-1470. [PMID: 29449623 DOI: 10.1038/s41366-018-0005-5] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Revised: 12/12/2017] [Accepted: 12/21/2017] [Indexed: 01/14/2023]
Abstract
BACKGROUND/OBJECTIVES Obesity is related to a dynamic extracellular matrix (ECM) remodeling, which involves the synthesis and degradation of different proteins, such as tenascin C (TNC) in the adipose tissue (AT). Given the functional relationship between leptin and inducible nitric oxide synthase (iNOS), our aim was to analyze the impact of the absence of the iNOS gene in AT inflammation and ECM remodeling in ob/ob mice. SUBJECTS/METHODS The expression of genes involved in inflammation and ECM remodeling was evaluated in 10-week-old male double knockout (DBKO) mice simultaneously lacking the ob and iNOS genes as well as in ob/ob mice classified into three groups [control, leptin-treated (1 mg kg-1 day-1) and pair-fed]. RESULTS Leptin deficiency increased inflammation and fibrosis in AT. As expected, leptin treatment improved the obesity phenotype. iNOS deficiency in ob/ob mice improved insulin sensitivity, AT inflammation, and ECM remodeling, as evidenced by lower AT macrophage infiltration and collagen deposition, a downregulation of proinflammatory and profibrogenic genes Tnf, Emr1, Hif1a, Col6a1, Col6a3, and Tnc, as well as lower circulating TNC levels. Interestingly, leptin upregulated TNC expression and release in 3T3-L1 adipocytes, and iNOS knockdown in 3T3-L1 fat cells produced a significant decrease in basal and leptin-induced Tnc expression. CONCLUSIONS Ablation of iNOS in leptin-deficient mice improved AT inflammation and ECM remodeling-related genes, attenuating fibrosis, and metabolic dysfunction. The activation of iNOS by leptin is necessary for the synthesis and secretion of TNC in adipocytes, suggesting an important role of this alarmin in the development of AT inflammation and fibrosis.
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Trejo-Vazquez F, Garza-Veloz I, Villela-Ramirez GA, Ortiz-Castro Y, Mauricio-Saucedo P, Cardenas-Vargas E, Diaz-Baez M, Cid-Baez MA, Castañeda-Miranda R, Ortiz-Rodriguez JM, Solis-Sanchez LO, Martinez-Fierro ML. Positive association between leptin serum levels and disease activity on endoscopy in inflammatory bowel disease: A case-control study. Exp Ther Med 2018; 15:3336-3344. [PMID: 29545852 PMCID: PMC5841033 DOI: 10.3892/etm.2018.5835] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Accepted: 11/17/2017] [Indexed: 12/13/2022] Open
Abstract
Inflammatory bowel disease (IBD) includes ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis. As these subtypes of IBD display important differences in the behavior of the natural course of the disease, the identification of non-invasive markers for IBD is important. The aim of the present study was to evaluate the serum levels of 10 adipokines and their association with endoscopic activity in IBD. The 10-protein profile (C-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, insulin, leptin, plasminogen activator inhibitor-1, resistin and visfatin) was evaluated using serum from 53 participants (23 UC and 11 CD patients, as well as 19 controls) from Zacatecas (Mexico) by using the Bio-Plex Pro Human Diabetes 10-Plex Panel (Bio-Rad Laboratories, Inc.). Compared with those in the controls, leptin levels were significantly lower in patients with IBD (P=4.9×10−4). In addition, serum leptin displayed differences between groups with and without disease activity on endoscopy (P<0.001). Among the study population, serum leptin levels of <5,494 pg/ml significantly increased the odds of IBD by 12.8-fold [odds ratio (OR)=12.8, 95% confidence interval (CI)=3.04–53.9, P=0.001]. In addition, patients with serum leptin levels of <2,498 pg/ml displayed 5.8-fold greater odds of disease activity on endoscopy among the study population (OR=5.8, 95% CI=1.52–22.4, P=0.013). No differences in the serum levels of the remaining proteins were identified between the groups. Among the study population, serum leptin was associated with an increased risk of IBD and with disease activity on endoscopy. Additional studies will be necessary to validate the use of leptin as a non-invasive biomarker of IBD severity.
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Affiliation(s)
- Fabiola Trejo-Vazquez
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas 'Francisco García Salinas', Zacatecas 98160, Mexico.,Department of Gastroenterology, Hospital General de Zacatecas, Instituto de Seguridad y Servicios Sociales Para Los Trabajadores del Estado, Zacatecas 98000, Mexico
| | - Idalia Garza-Veloz
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas 'Francisco García Salinas', Zacatecas 98160, Mexico.,Bioengineering Laboratory, Unidad Academica de Ingenieria Electrica, Universidad Autonoma de Zacatecas, Zacatecas 98000, Mexico
| | - Gabriela Alejandra Villela-Ramirez
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas 'Francisco García Salinas', Zacatecas 98160, Mexico.,Bioengineering Laboratory, Unidad Academica de Ingenieria Electrica, Universidad Autonoma de Zacatecas, Zacatecas 98000, Mexico
| | - Yolanda Ortiz-Castro
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas 'Francisco García Salinas', Zacatecas 98160, Mexico
| | - Panfilo Mauricio-Saucedo
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas 'Francisco García Salinas', Zacatecas 98160, Mexico.,Departamento de Enseñanza e Investigación, Hospital General Zacatecas 'Luz González Cosío', Servicios de Salud de Zacatecas, Zacatecas 98160, Mexico
| | - Edith Cardenas-Vargas
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas 'Francisco García Salinas', Zacatecas 98160, Mexico.,Departamento de Enseñanza e Investigación, Hospital General Zacatecas 'Luz González Cosío', Servicios de Salud de Zacatecas, Zacatecas 98160, Mexico
| | - Mariana Diaz-Baez
- Department of Gastroenterology, Hospital General de Zacatecas, Instituto de Seguridad y Servicios Sociales Para Los Trabajadores del Estado, Zacatecas 98000, Mexico
| | - Miguel A Cid-Baez
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas 'Francisco García Salinas', Zacatecas 98160, Mexico.,Bioengineering Laboratory, Unidad Academica de Ingenieria Electrica, Universidad Autonoma de Zacatecas, Zacatecas 98000, Mexico
| | - Rodrigo Castañeda-Miranda
- Bioengineering Laboratory, Unidad Academica de Ingenieria Electrica, Universidad Autonoma de Zacatecas, Zacatecas 98000, Mexico
| | - Jose Manuel Ortiz-Rodriguez
- Bioengineering Laboratory, Unidad Academica de Ingenieria Electrica, Universidad Autonoma de Zacatecas, Zacatecas 98000, Mexico
| | - Luis Octavio Solis-Sanchez
- Bioengineering Laboratory, Unidad Academica de Ingenieria Electrica, Universidad Autonoma de Zacatecas, Zacatecas 98000, Mexico
| | - Margarita L Martinez-Fierro
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas 'Francisco García Salinas', Zacatecas 98160, Mexico.,Bioengineering Laboratory, Unidad Academica de Ingenieria Electrica, Universidad Autonoma de Zacatecas, Zacatecas 98000, Mexico
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Machado MV, Diehl AM. Pathogenesis of Nonalcoholic Fatty Liver Disease. ZAKIM AND BOYER'S HEPATOLOGY 2018:369-390.e14. [DOI: 10.1016/b978-0-323-37591-7.00025-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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47
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Liu JL, Yang LC, Zhu XJ, Wang WJ, Zheng GD. Combinational Effect of Pine Needle Polysaccharide and Kudzu Flavonoids on Cell Differentiation and Fat Metabolism in 3T3-L1 Cells. FOOD SCIENCE AND TECHNOLOGY RESEARCH 2018. [DOI: 10.3136/fstr.24.903] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Affiliation(s)
- Ji-Luan Liu
- Jiangxi Key Laboratory of Natural Product and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University
| | - Li-Cong Yang
- Jiangxi Key Laboratory of Natural Product and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University
| | - Xiao-Juan Zhu
- Jiangxi Key Laboratory of Natural Product and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University
| | - We-Jun Wang
- Jiangxi Key Laboratory of Natural Product and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University
| | - Guo-Dong Zheng
- Jiangxi Key Laboratory of Natural Product and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University
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Seyam E, Hasan M, Khalifa EM, Ramadan A, Hefzy E. Evaluation of tumor necrosis factor alpha serum level in obese and lean women with clomiphene citrate-resistant polycystic ovary disease. Gynecol Endocrinol 2017; 33:892-898. [PMID: 28480767 DOI: 10.1080/09513590.2017.1320383] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
OBJECTIVE The aim of this work was to investigate the level of the serum level of tumor necrosis factor alpha (TNF-α) as an inflammatory biomarker in lean and obese women with polycystic ovary disease (PCOD), who are resistant to clomiphene citrate (CCR-PCOD). PATIENTS AND DESIGN It is a case-controlled study, where 150 (n = 150) PCOD women (study group), who are resistant to clomiphene citrate (CCR-PCOD) had been recruited, in addition to 100 (n = 100) women with PCOD, who are not resistant to clomiphene citrate (NCCR-PCOD) as the first control group, and another 100 women (n = 100) fertile women with normal reproductive health, as the second control group. All the recruited subjects had been divided into subgroups according to the BMI: One obese group with BMI ≥ 27 and the second lean group with BMI < 27. TNF-α had been measured in all women groups recruited, in addition to the other essential, basic and PCOD-relevant biochemical and hormonal tests. RESULTS TNF-α level was found to be higher in all PCOD women, either the study or control PCOD groups, than the fertile control group (49.93 ± 3.39 versus 35.83 ± 2.47 pg/ml, p < 0.001). The level of TNF-α has come highest in the obese clomiphene citrate-resistant PCOD women (obese CCR-PCOD), while the lowest has come in the lean PCOD women, who are not resistant to clomiphene citrate (NCCR-PCOD). Free Androgen Index (FAI) and androgenic obesity with higher W/H ratio were clearly going with TNF-α pattern and have come higher in all PCOD compared to the fertile control group. Insulin resistance (IR) shows a positive correlation with BMI regardless off PCOD status and androgen level as well. The level of other basic and PCOD-relevant hormones like FSH, TSH and prolactin have never shown statistically significant differences between all the study and control groups, except LH serum level which has shown a nonsignificant higher level in all PCOD women included either resistant to CC or not. CONCLUSION TNF-α serum level has come significantly higher in all women with PCOD, especially in those resistant to CC. Androgenic obesity with higher W/H ratio has shown a positive correlation with TNF-α level, which could consider it a good severity index of PCOD status and an informative predictor of CCR before its use.
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Affiliation(s)
- Emaduldin Seyam
- a Obstetrics and Gynecology Department , Minia University College of Medicine , Minia , Egypt
| | - Momen Hasan
- a Obstetrics and Gynecology Department , Minia University College of Medicine , Minia , Egypt
| | - Eissa M Khalifa
- a Obstetrics and Gynecology Department , Minia University College of Medicine , Minia , Egypt
| | - Ahmad Ramadan
- b Obstetrics and Gynecology Department , Minia General Hospital , Minia , Egypt
| | - Enas Hefzy
- c Microbiology and Immunology Department , Fayoum University College of Medicine , Fayoum , Egypt
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Abd El Aal HA, Ahmed LA, Hassan WA, Fawzy HM, Moawad H. Combination of carvacrol with simvastatin improves the lipid-lowering efficacy and alleviates simvastatin side effects. J Biochem Mol Toxicol 2017; 31. [PMID: 29071762 DOI: 10.1002/jbt.21981] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Revised: 08/13/2017] [Accepted: 08/19/2017] [Indexed: 01/08/2023]
Abstract
The present investigation was designed to examine the possible additive hypolipidemic effect of carvacrol (CARV) in combination with simvastatin (SIM) on poloxamer 407 (P407)-induced hyperlipidemia. Rats were injected with P407, (500 mg/ kg; i.p.), twice a week, for 30 days. Treatment was carried out by administration of SIM (20 mg/kg/day; p.o.) or CARV (50 mg/kg/day; p.o.) or combination of them. Treatment with CARV significantly decreased total cholesterol, triglycerides, low-density lipoprotein, atherogenic index, leptin, and increased high-density lipoprotein and adiponectin. Moreover, CARV potentiated the hypolipidemic effect of SIM. Both SIM and CARV alleviated the oxidative stress induced by P407. Interestingly, CARV, when combined with SIM, significantly ameliorated SIM-induced liver and muscle injury by reducing the level of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and myoglobin and restoring the normal histological picture of both liver and muscle as well as apoptosis.
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Affiliation(s)
- Hayat A Abd El Aal
- Department of Pharmacology, National Organization for Drug Control and Research, NODCAR, Giza, Egypt
| | - Lamiaa A Ahmed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Wedad A Hassan
- Department of Pharmacology, National Organization for Drug Control and Research, NODCAR, Giza, Egypt
| | - Hala M Fawzy
- Department of Pharmacology, National Organization for Drug Control and Research, NODCAR, Giza, Egypt
| | - Helmy Moawad
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
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Hayward CE, Cowley EJ, Sibley CP, Myers JE, Wareing M. Exposure to omentum adipose tissue conditioned medium from obese pregnant women promotes myometrial artery dysfunction. J Obstet Gynaecol Res 2017; 44:124-133. [PMID: 29027317 PMCID: PMC5813134 DOI: 10.1111/jog.13482] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Accepted: 07/17/2017] [Indexed: 12/19/2022]
Abstract
Aim Underlying mechanisms of poor pregnancy outcome in obese (OB) mothers (body mass index [BMI] ≥ 30 kg/m2) are unknown. Our studies demonstrate that OB pregnant women have altered myometrial artery (MA) function related to the thromboxane and nitric oxide pathways. In obesity, increased central fat mass is associated with an altered endocrine milieu. We tested the hypothesis that in OB pregnant women the omentum, a central fat store, releases factors that promote dysfunction in normal MAs. Methods Myometrial and omental adipose tissue biopsies were obtained from women with uncomplicated term pregnancies. Omental adipose tissue explants from six normal weight (NW; BMI 18.5–24.9 kg/m2) and six OB (BMI ≥ 30 kg/m2) women were cultured and the conditioned medium collected and pooled to produce NW medium and OB medium. Adipokine concentrations were measured using enzyme‐linked immunosorbent assays. Wire myography was used to assess the effect of conditioned medium (NW or OB; N = 7) or leptin (100 nM; N = 5) exposure on MA responses to U46619 (thromboxane‐mimetic) and bradykinin (endothelial‐dependent vasodilator). Results OB medium had higher leptin and lower adiponectin levels than NW medium. U46619 and bradykinin concentration response curves shifted upwards in MAs exposed to OB medium but were unaffected by leptin. Conclusions Omental adipose tissue from OB pregnant women produced altered concentrations of adipokines. Acute OB medium exposure induced MA dysfunction, an effect not mirrored by exposure to leptin. These data suggest that an aberrant endocrine environment created by increased central adiposity in OB pregnant women induces vascular endothelial dysregulation, which may predispose them to a poor pregnancy outcome.
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Affiliation(s)
- Christina E Hayward
- Maternal and Fetal Health Research Centre, Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.,St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
| | - Elizabeth J Cowley
- Maternal and Fetal Health Research Centre, Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.,St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
| | - Colin P Sibley
- Maternal and Fetal Health Research Centre, Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.,St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
| | - Jenny E Myers
- Maternal and Fetal Health Research Centre, Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.,St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
| | - Mark Wareing
- Maternal and Fetal Health Research Centre, Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.,St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
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