|
1
|
Zhou H, Gizlenci M, Xiao Y, Martin F, Nakamori K, Zicari EM, Sato Y, Tullius SG. Obesity-associated Inflammation and Alloimmunity. Transplantation 2025; 109:588-596. [PMID: 39192462 PMCID: PMC11868468 DOI: 10.1097/tp.0000000000005183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2024]
Abstract
Obesity is a worldwide health problem with a rapidly rising incidence. In organ transplantation, increasing numbers of patients with obesity accumulate on waiting lists and undergo surgery. Obesity is in general conceptualized as a chronic inflammatory disease, potentially impacting alloimmune response and graft function. Here, we summarize our current understanding of cellular and molecular mechanisms that control obesity-associated adipose tissue inflammation and provide insights into mechanisms affecting transplant outcomes, emphasizing on the beneficial effects of weight loss on alloimmune responses.
Collapse
Affiliation(s)
- Hao Zhou
- Division of Transplant Surgery & Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
| | - Merih Gizlenci
- Division of Transplant Surgery & Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
- Department of General, Visceral, Cancer and Transplant Surgery, University Hospital of Cologne, Cologne, Germany
| | - Yao Xiao
- Division of Transplant Surgery & Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
| | - Friederike Martin
- Division of Transplant Surgery & Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
- Department of Surgery, CVK/CCM, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Keita Nakamori
- Division of Transplant Surgery & Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
- Department of Urology, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
| | - Elizabeth M. Zicari
- Division of Transplant Surgery & Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
- Faculté de Pharmacie, Université Paris Cité, Paris, France
| | - Yuko Sato
- Division of Transplant Surgery & Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
| | - Stefan G. Tullius
- Division of Transplant Surgery & Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
| |
Collapse
|
|
2
|
Pu J, Yang X, Lin TT, Fillmore TL, Gritsenko MA, Kelly SS, Swensen AC, Shi T, Master SR, DeLany JP, Goodpaster BH, Qian WJ, Qu J. A multiplex assay of leptin, resistin, and adiponectin by immunoaffinity enrichment and targeted mass spectrometry. J Mass Spectrom Adv Clin Lab 2025; 36:11-18. [PMID: 40093568 PMCID: PMC11910354 DOI: 10.1016/j.jmsacl.2025.01.003] [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: 07/14/2024] [Revised: 01/18/2025] [Accepted: 01/31/2025] [Indexed: 03/19/2025] Open
Abstract
Background Leptin, resistin, and adiponectin are critical adipokines involved in the pathophysiology of obesity and its related disorders, including type 2 diabetes. Although these biomarkers have historically been quantified using immunoassays, the specificity of antibody-based methods has frequently been questioned. As a result, there is an increasing interest in developing reliable, multiplexed clinical assays that utilize mass spectrometry for improved accuracy. In this study, we present a multiplexed immunoaffinity liquid chromatography-tandem mass spectrometry (multi-IA-LC-MS/MS) assay designed for the sensitive and selective measurement of leptin, resistin, and adiponectin in human plasma. Methods Leptin, resistin, and adiponectin were selectively enriched from plasma samples using an antibody cocktail composed of monoclonal antibodies targeting each respective adipokine. The enriched adipokines underwent enzymatic digestion, and the resulting tryptic peptides were quantified using LC-MS/MS. The validated assay was subsequently applied to plasma samples collected from a cohort of subjects representing various weight categories, including normal weight, overweight, and obesity. Results The lower limits of quantification for the assay were determined to be 0.5 ng/mL for both leptin and resistin, and 50 ng/mL for adiponectin. Intra- day, inter- day, and total imprecision measurements were all < 15 %, while spike recovery consistently exceeded 83 %. Comparative analysis with individual immunoassays demonstrated strong correlation, with all correlation coefficients (r) being equal to or greater than 0.869. Notably, when comparing subjects with obesity to those with normal weight, there was an approximately nine-fold increase in circulating leptin levels and a ∼1.6-fold decrease in circulating adiponectin levels. Conclusions A multi-IA-LC-MS/MS assay was developed for the simultaneous and sensitive measurement of leptin, resistin, and adiponectin in clinical samples. This quantitative method shows significant potential for applications related to obesity and could facilitate improved clinical management and understanding of obesity-related conditions.
Collapse
Affiliation(s)
- Jie Pu
- Department of Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, United States
| | - Xinxin Yang
- Department of Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, United States
| | - Tai-Tu Lin
- Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, United States
| | - Thomas L Fillmore
- Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, United States
| | - Marina A Gritsenko
- Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, United States
| | - Shane S Kelly
- Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, United States
| | - Adam C Swensen
- Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, United States
| | - Tujin Shi
- Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, United States
| | - Stephen R Master
- Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, United States
| | - James P DeLany
- AdventHealth, Translational Research Institute, Orlando, FL, United States
| | - Bret H Goodpaster
- AdventHealth, Translational Research Institute, Orlando, FL, United States
| | - Wei-Jun Qian
- Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, United States
| | - Jun Qu
- Department of Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, United States
- New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, United States
| |
Collapse
|
|
3
|
Kawamoto R, Kikuchi A, Ninomiya D, Kumagi T, Abe M. Alcohol consumption and high-molecular-weight adiponectin levels are interactively associated with all-cause mortality among community-dwelling persons. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2025. [PMID: 40156115 DOI: 10.1111/acer.70037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 03/02/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND Decreased levels of high-molecular-weight (HMW) adiponectin are associated with metabolic syndrome and insulin resistance. This relationship may be further confounded by alcohol consumption, which plays a role in the development of liver dysfunction. In Japan, few studies have investigated the relationship between HMW adiponectin levels and alcohol consumption with mortality. METHODS The study included 845 male participants (mean age, 61 ± 13 years; range, 20-89 years) and 1065 female participants (mean age, 63 ± 11 years; range, 22-88 years). Of the participants, 809 (42.4%) were classified as nondrinkers, 561 (29.4%) as occasional drinkers, 346 (18.1%) as daily light drinkers, and 194 (10.2%) as daily heavy drinkers. A Cox proportional hazards model was used to calculate hazard ratios (HR) for all-cause mortality, adjusting for various confounders, including HMW adiponectin levels. RESULTS Individuals who abstained from alcohol consumption (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.00-1.52) or engaged in daily heavy drinking (HR, 1.39; 95% CI, 1.04-1.86) exhibited significantly higher overall mortality than occasional drinkers. Additionally, those with the 3rd standard deviation (SD) level of HMW adiponectin (HR, 1.39; 95% CI, 1.07-1.80) and 4th SD level (HR, 1.65; 95% CI, 1.23-2.23) had a similarly increased risk of all-cause mortality compared to those with the lowest levels. After adjusting for confounders, the HR for individuals with the 3rd + 4th SD levels of HMW adiponectin was significantly elevated in nondrinkers (HR, 1.89; 95% CI, 1.09-3.29), occasional drinkers (HR, 1.84; 95% CI, 1.05-3.21), and daily heavy drinkers (HR, 1.90; 95% CI, 1.05-3.44), but not in daily light drinkers. The interaction between alcohol consumption and HMW adiponectin levels was significantly associated with all-cause mortality. CONCLUSION These findings suggest that alcohol consumption and elevated HMW adiponectin levels are interactively associated with all-cause mortality in community-dwelling individuals.
Collapse
Affiliation(s)
- Ryuichi Kawamoto
- Department of Community Medicine, Ehime University Graduate School of Medicine, Toon-City, Ehime, Japan
- Department of Internal Medicine, Seiyo Municipal Nomura Hospital, Seiyo-City, Ehime, Japan
| | - Asuka Kikuchi
- Department of Community Medicine, Ehime University Graduate School of Medicine, Toon-City, Ehime, Japan
- Department of Internal Medicine, Seiyo Municipal Nomura Hospital, Seiyo-City, Ehime, Japan
| | - Daisuke Ninomiya
- Department of Community Medicine, Ehime University Graduate School of Medicine, Toon-City, Ehime, Japan
- Department of Internal Medicine, Seiyo Municipal Nomura Hospital, Seiyo-City, Ehime, Japan
| | - Teru Kumagi
- Department of Community Medicine, Ehime University Graduate School of Medicine, Toon-City, Ehime, Japan
| | - Masanori Abe
- Department of Community Medicine, Ehime University Graduate School of Medicine, Toon-City, Ehime, Japan
| |
Collapse
|
|
4
|
Ueda H, Mineo R, Sugiyama T, Koseki M, Itoh Y, Iwamoto R, Tamba S, Yamamoto K, Yamada Y, Hiraoka H, Matsuzawa Y. A Man with Primary Hyperchylomicronemia with Triglyceride Levels Exceeding 11,000 mg/dL Was Well Controlled by Pemafibrate Combined with Dietary Therapy. Intern Med 2025; 64:741-747. [PMID: 39048362 PMCID: PMC11949665 DOI: 10.2169/internalmedicine.3946-24] [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: 04/05/2024] [Accepted: 06/05/2024] [Indexed: 07/27/2024] Open
Abstract
A 50-year-old man with a triglyceride (TG) level of 11,397 mg/dL was admitted to our hospital. He consumed a high-fat and high-carbohydrate diet as well as more than 100 g of alcohol per day. He had type 2 diabetes and obesity and had previously suffered from severe acute pancreatitis twice. A genetic analysis revealed compound heterozygous mutations in APOA5 (c.56C>G and c.553G>T). In addition to low-fat meals and alcohol cessation, administration of pemafibrate lowered his triglyceride levels to <150 mg/dL.
Collapse
Affiliation(s)
- Hiroyuki Ueda
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Japan
| | - Ryohei Mineo
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Japan
| | - Takuya Sugiyama
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Japan
| | - Masahiro Koseki
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Japan
| | - Yoshito Itoh
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Japan
| | - Ryuya Iwamoto
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Japan
| | - Sachiko Tamba
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Japan
| | - Koji Yamamoto
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Japan
| | - Yuya Yamada
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Japan
| | | | - Yuji Matsuzawa
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Japan
| |
Collapse
|
|
5
|
Klobučar I, Habisch H, Klobučar L, Trbušić M, Pregartner G, Berghold A, Kostner GM, Scharnagl H, Madl T, Frank S, Degoricija V. Sex-Related Differences in the Associations between Adiponectin and Serum Lipoproteins in Healthy Subjects and Patients with Metabolic Syndrome. Biomedicines 2024; 12:1972. [PMID: 39335486 PMCID: PMC11429094 DOI: 10.3390/biomedicines12091972] [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: 07/26/2024] [Revised: 08/23/2024] [Accepted: 08/28/2024] [Indexed: 09/30/2024] Open
Abstract
The strong associations between the serum levels of adiponectin and the lipoprotein subclasses observed in healthy subjects are much weaker in patients with metabolic syndrome (MS). However, the impact of sex on these associations remained unexplored. Therefore, in the present study, we examined associations between adiponectin and the lipoprotein subclasses, analyzed by nuclear magnetic resonance spectroscopy, separately in healthy females and males, as well as in females and males with MS. We observed negative correlations between adiponectin and VLDL, IDL, and small-dense LDL in healthy males, but neither in healthy females nor in females or males with MS. Additionally, adiponectin was positively correlated with some HDL subclasses in healthy males and females with MS, but not in healthy females or males with MS. Adjusting for age and either body mass index, waist circumference, C-reactive protein, or interleukin-6 weakened the associations between adiponectin and VLDL and IDL but not small-dense LDL. The adjustment weakened the associations between adiponectin and HDL in healthy males but not in females with MS. Based on our results, we conclude that sex and the presence of MS are strong determinants of the associations between adiponectin and serum lipoproteins and that the complex regulatory network comprising adiponectin and other molecular players involved in the regulation of lipoprotein metabolism is primarily operative in healthy males and females with MS.
Collapse
Affiliation(s)
- Iva Klobučar
- Department of Cardiology, Sisters of Charity University Hospital Centre, 10000 Zagreb, Croatia; (I.K.); (M.T.)
| | - Hansjörg Habisch
- Otto Loewi Research Center, Medicinal Chemistry, Medical University of Graz, 8010 Graz, Austria; (H.H.); (T.M.)
| | - Lucija Klobučar
- Department of Medicine, University Hospital Centre Osijek, 31000 Osijek, Croatia;
| | - Matias Trbušić
- Department of Cardiology, Sisters of Charity University Hospital Centre, 10000 Zagreb, Croatia; (I.K.); (M.T.)
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia;
| | - Gudrun Pregartner
- Institute for Medical Informatics, Statistics, and Documentation, Medical University of Graz, 8036 Graz, Austria; (G.P.); (A.B.)
| | - Andrea Berghold
- Institute for Medical Informatics, Statistics, and Documentation, Medical University of Graz, 8036 Graz, Austria; (G.P.); (A.B.)
| | - Gerhard M. Kostner
- Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria;
| | - Hubert Scharnagl
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8036 Graz, Austria;
| | - Tobias Madl
- Otto Loewi Research Center, Medicinal Chemistry, Medical University of Graz, 8010 Graz, Austria; (H.H.); (T.M.)
- BioTechMed-Graz, 8010 Graz, Austria
| | - Saša Frank
- Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria;
- BioTechMed-Graz, 8010 Graz, Austria
| | - Vesna Degoricija
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia;
- Department of Medicine, Sisters of Charity University Hospital Centre, 10000 Zagreb, Croatia
| |
Collapse
|
|
6
|
Singhal AK, Singh G, Singh SK, Karunanand B, Gunjan G, Agrawal SK. Exploring the link between leptin levels and metabolic syndrome in elderly Indian patients: Implications for family medicine and primary care practices. J Family Med Prim Care 2024; 13:3633-3638. [PMID: 39464951 PMCID: PMC11504790 DOI: 10.4103/jfmpc.jfmpc_2008_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Revised: 01/17/2024] [Accepted: 02/19/2024] [Indexed: 10/29/2024] Open
Abstract
Background The metabolic syndrome (MetS), according to the Adult Treatment Panel III of the National Cholesterol Education Programme, is a collection of metabolic abnormalities that includes one, two, or all three of the following traits: obesity in the abdomen, dyslipidemia, hypertension, fasting blood sugar, or insulin resistance. This study's aim was to assess the relationship between fasting serum leptin and MetS in elderly adults with T2DM in the Northern Indian population. Material and Methods The following information was collected from all the participants: (1) anthropometric data, (2) biochemical data, and (3) a lifestyle questionnaire on sociodemographic data, dietary practices, smoking, and alcohol intake to identify their risk factors for diabetes mellitus, CVD, and hypertension. Results A total of 36 older participants (56.30%) had a history of hypertension, while 29 elderly participants (44.61%) had diabetes mellitus. A total of 32 elderly participants (49.2%) had MetS, and this group had higher serum leptin (P 0.003), body weight (P = 0.019), BMI (P 0.001), waist circumference (P 0.001), CRP (P = 0.021), insulin (P = 0.001), and HOMA-IR (P = 0.003) values as well as higher percentages of females (P = 0.001), and those with type 2 diabetes mellitus (P = 0.002) and hypertension (P = 0.039) than those in the non-MetS group. Conclusion In older persons with T2DM, our study discovered a favorable correlation between serum leptin and MetS. It can act as a standalone indicator of MetS, offering a way to spot populations at risk for associated consequences and enabling early intervention.
Collapse
Affiliation(s)
- Arjun Kumar Singhal
- Department of Biochemistry, Faculty of Medicine and Health Sciences, SGT, Gurugram, Haryana, India
| | - Gaurav Singh
- Department of Microbiology, ESIC Medical College and Hospital, Patna, Bihar, India
| | - Shravan Kumar Singh
- Department of Medical Health and Family Welfare, Plibhit, Uttar Pradesh, India
| | - Busi Karunanand
- Department of Biochemistry, Faculty of Medicine and Health Sciences, SGT, Gurugram, Haryana, India
| | - Gagan Gunjan
- Department of General Medicine, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India
| | - Sonu K. Agrawal
- Consultant Microbiologist, Vimta Labs. Limited, New Delhi, India
| |
Collapse
|
|
7
|
Sigdel S, Udoh G, Albalawy R, Wang J. Perivascular Adipose Tissue and Perivascular Adipose Tissue-Derived Extracellular Vesicles: New Insights in Vascular Disease. Cells 2024; 13:1309. [PMID: 39195199 PMCID: PMC11353161 DOI: 10.3390/cells13161309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 07/29/2024] [Accepted: 08/02/2024] [Indexed: 08/29/2024] Open
Abstract
Perivascular adipose tissue (PVAT) is a special deposit of fat tissue surrounding the vasculature. Previous studies suggest that PVAT modulates the vasculature function in physiological conditions and is implicated in the pathogenesis of vascular diseases. Understanding how PVAT influences vasculature function and vascular disease progression is important. Extracellular vesicles (EVs) are novel mediators of intercellular communication. EVs encapsulate molecular cargo such as proteins, lipids, and nucleic acids. EVs can influence cellular functions by transferring the carried bioactive molecules. Emerging evidence indicates that PVAT-derived EVs play an important role in vascular functions under health and disease conditions. This review will focus on the roles of PVAT and PVAT-EVs in obesity, diabetic, and metabolic syndrome-related vascular diseases, offering novel insights into therapeutic targets for vascular diseases.
Collapse
Affiliation(s)
- Smara Sigdel
- Department of Biomedical Sciences, Joan C Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA; (S.S.); (G.U.)
| | - Gideon Udoh
- Department of Biomedical Sciences, Joan C Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA; (S.S.); (G.U.)
| | - Rakan Albalawy
- Department of Internal Medicine, Joan C Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA;
| | - Jinju Wang
- Department of Biomedical Sciences, Joan C Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA; (S.S.); (G.U.)
| |
Collapse
|
|
8
|
Savulescu-Fiedler I, Mihalcea R, Dragosloveanu S, Scheau C, Baz RO, Caruntu A, Scheau AE, Caruntu C, Benea SN. The Interplay between Obesity and Inflammation. Life (Basel) 2024; 14:856. [PMID: 39063610 PMCID: PMC11277997 DOI: 10.3390/life14070856] [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: 05/28/2024] [Revised: 07/01/2024] [Accepted: 07/05/2024] [Indexed: 07/28/2024] Open
Abstract
Obesity is an important condition affecting the quality of life of numerous patients and increasing their associated risk for multiple diseases, including tumors and immune-mediated disorders. Inflammation appears to play a major role in the development of obesity and represents a central point for the activity of cellular and humoral components in the adipose tissue. Macrophages play a key role as the main cellular component of the adipose tissue regulating the chronic inflammation and modulating the secretion and differentiation of various pro- and anti-inflammatory cytokines. Inflammation also involves a series of signaling pathways that might represent the focus for new therapies and interventions. Weight loss is essential in decreasing cardiometabolic risks and the degree of associated inflammation; however, the latter can persist for long after the excess weight is lost, and can involve changes in macrophage phenotypes that can ensure the metabolic adjustment. A clear understanding of the pathophysiological processes in the adipose tissue and the interplay between obesity and chronic inflammation can lead to a better understanding of the development of comorbidities and may ensure future targets for the treatment of obesity.
Collapse
Affiliation(s)
- Ilinca Savulescu-Fiedler
- Department of Internal Medicine, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Internal Medicine and Cardiology, Coltea Clinical Hospital, 030167 Bucharest, Romania
| | - Razvan Mihalcea
- Department of Internal Medicine and Cardiology, Coltea Clinical Hospital, 030167 Bucharest, Romania
| | - Serban Dragosloveanu
- Department of Orthopaedics, “Foisor” Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, 021382 Bucharest, Romania
- Department of Orthopaedics and Traumatology, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Cristian Scheau
- Department of Physiology, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania (C.C.)
- Department of Radiology and Medical Imaging, “Foisor” Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, 030167 Bucharest, Romania
| | - Radu Octavian Baz
- Clinical Laboratory of Radiology and Medical Imaging, “Sf. Apostol Andrei” County Emergency Hospital, 900591 Constanta, Romania
- Department of Radiology and Medical Imaging, Faculty of Medicine, “Ovidius” University, 900527 Constanta, Romania
| | - Ana Caruntu
- Department of Oral and Maxillofacial Surgery, “Carol Davila” Central Military Emergency Hospital, 010825 Bucharest, Romania
- Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, “Titu Maiorescu” University, 031593 Bucharest, Romania
| | - Andreea-Elena Scheau
- Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Constantin Caruntu
- Department of Physiology, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania (C.C.)
- Department of Dermatology, “Prof. N.C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 011233 Bucharest, Romania
| | - Serban Nicolae Benea
- Department of Infectious Diseases, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- “Prof. Dr. Matei Balș” National Institute for Infectious Diseases, 021105 Bucharest, Romania
| |
Collapse
|
|
9
|
El Assar M, Rodríguez-Sánchez I, Álvarez-Bustos A, Rodríguez-Mañas L. Biomarkers of frailty. Mol Aspects Med 2024; 97:101271. [PMID: 38631189 DOI: 10.1016/j.mam.2024.101271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 03/19/2024] [Accepted: 03/20/2024] [Indexed: 04/19/2024]
Abstract
Several biomarkers have been proposed to identify frailty, a multisystemic age-related syndrome. However, the complex pathophysiology and the absence of a consensus on a comprehensive and universal definition make it challenging to pinpoint a singular biomarker or set of biomarkers that conclusively characterize frailty. This review delves into the main laboratory biomarkers, placing special emphasis on those associated with various pathways closely tied to the frailty condition, such as inflammation, oxidative stress, mitochondrial dysfunction, metabolic and endocrine alterations and microRNA. Additionally, we provide a summary of different clinical biomarkers encompassing different tools that have been proposed to assess frailty. We further address various imaging biomarkers such as Dual Energy X-ray Absorptiometry, Bioelectrical Impedance analysis, Computed Tomography and Magnetic Resonance Imaging, Ultrasound and D3 Creatine dilution. Intervention to treat frailty, including non-pharmacological ones, especially those involving physical exercise and nutrition, and pharmacological interventions, that include those targeting specific mechanisms such as myostatin inhibitors, insulin sensitizer metformin and with special relevance for hormonal treatments are mentioned. We further address the levels of different biomarkers in monitoring the potential positive effects of some of these interventions. Despite the availability of numerous biomarkers, their performance and usefulness in the clinical arena are far from being satisfactory. Considering the multicausality of frailty, there is an increasing need to assess the role of sets of biomarkers and the combination between laboratory, clinical and image biomarkers, in terms of sensitivity, specificity and predictive values for the diagnosis and prognosis of the different outcomes of frailty to improve detection and monitoring of older people with frailty or at risk of developing it, being this a need in the everyday clinical practice.
Collapse
Affiliation(s)
- Mariam El Assar
- Fundación para la Investigación Biomédica del Hospital Universitario de Getafe, Madrid, Spain; Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain
| | | | - Alejandro Álvarez-Bustos
- Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain
| | - Leocadio Rodríguez-Mañas
- Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain; Servicio de Geriatría, Hospital Universitario de Getafe, Madrid, Spain.
| |
Collapse
|
|
10
|
Iwamura N, Kidoguchi S, Asahi N, Takeda I, Matsuta K, Miyagi K, Iwano M, Miyazaki R, Kimura H. Superiority of high sensitivity cardiac troponin I over NT-proBNP and adiponectin for 7-year mortality in stable patients receiving haemodialysis. Sci Rep 2024; 14:11488. [PMID: 38769120 PMCID: PMC11106234 DOI: 10.1038/s41598-024-62491-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 05/17/2024] [Indexed: 05/22/2024] Open
Abstract
Patients on haemodialysis (HD) have high mortality risk, and prognostic values of the major cardiovascular biomarkers cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), and adiponectin should be ascertained over longer follow-up periods using higher-sensitivity assays, which we undertook. In 221 HD patients, levels of high-sensitivity (hs)-cTnI, NT-proBNP, and adiponectin, were measured using high-sensitivity assays, and their associations with all-cause mortality (ACM) and cardiovascular mortality (CVM) were prospectively investigated for 7 years. Higher hs-cTnI and NT-proBNP levels were significant risk factors for ACM and CVM in the Kaplan-Meier analysis. Multivariate Cox proportional hazards analyses in a model including hs-cTnI and NT-proBNP identified log hs-cTnI, but not log NT-proBNP, as an independent risk factor for ACM (HR 2.12, P < 0.02) and CVM (HR 4.48, P < 0.0005). Stepwise analyses identified a high hs-cTnI tertile as a risk factor for ACM (HR 2.31, P < 0.01) and CVM (HR 6.70, P < 0.001). The addition of hs-cTnI to a model including age, CRP, DM, and NT-proBNP significantly improved the discrimination of ACM and CVM each over 7 years. Conclusively, hs-cTnI was superior to NT-proBNP and adiponectin in predicting ACM and CVM over 7 years in HD patients, suggesting the significance of baseline hs-cTnI measurements in long-term management.
Collapse
Affiliation(s)
- Nanami Iwamura
- Department of Clinical Laboratory, University of Fukui Hospital, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Yoshida, Fukui, 910-1193, Japan
| | - Shuhei Kidoguchi
- Department of Clinical Laboratory, University of Fukui Hospital, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Yoshida, Fukui, 910-1193, Japan
| | - Nanae Asahi
- Department of Clinical Laboratory, University of Fukui Hospital, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Yoshida, Fukui, 910-1193, Japan
| | - Izumi Takeda
- Department of Clinical Laboratory, University of Fukui Hospital, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Yoshida, Fukui, 910-1193, Japan
| | - Kohei Matsuta
- Department of Clinical Laboratory, University of Fukui Hospital, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Yoshida, Fukui, 910-1193, Japan
| | - Kyoko Miyagi
- Department of Internal Medicine, Fujita Memorial Hospital, Fukui, Japan
| | - Masayuki Iwano
- Division of Nephrology, Department of General Medicine, School of Medicine, University of Fukui, Fukui, Japan
| | - Ryoichi Miyazaki
- Department of Internal Medicine, Fujita Memorial Hospital, Fukui, Japan
| | - Hideki Kimura
- Department of Clinical Laboratory, University of Fukui Hospital, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Yoshida, Fukui, 910-1193, Japan.
| |
Collapse
|
|
11
|
Klobučar I, Habisch H, Klobučar L, Trbušić M, Pregartner G, Berghold A, Kostner GM, Scharnagl H, Madl T, Frank S, Degoricija V. Serum Levels of Adiponectin Are Strongly Associated with Lipoprotein Subclasses in Healthy Volunteers but Not in Patients with Metabolic Syndrome. Int J Mol Sci 2024; 25:5050. [PMID: 38732266 PMCID: PMC11084877 DOI: 10.3390/ijms25095050] [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: 03/22/2024] [Revised: 05/03/2024] [Accepted: 05/03/2024] [Indexed: 05/13/2024] Open
Abstract
Metabolic syndrome (MS) is a widespread disease in developed countries, accompanied, among others, by decreased adiponectin serum levels and perturbed lipoprotein metabolism. The associations between the serum levels of adiponectin and lipoproteins have been extensively studied in the past under healthy conditions, yet it remains unexplored whether the observed associations also exist in patients with MS. Therefore, in the present study, we analyzed the serum levels of lipoprotein subclasses using nuclear magnetic resonance spectroscopy and examined their associations with the serum levels of adiponectin in patients with MS in comparison with healthy volunteers (HVs). In the HVs, the serum levels of adiponectin were significantly negatively correlated with the serum levels of large buoyant-, very-low-density lipoprotein, and intermediate-density lipoprotein, as well as small dense low-density lipoprotein (LDL) and significantly positively correlated with large buoyant high-density lipoprotein (HDL). In patients with MS, however, adiponectin was only significantly correlated with the serum levels of phospholipids in total HDL and large buoyant LDL. As revealed through logistic regression and orthogonal partial least-squares discriminant analyses, high adiponectin serum levels were associated with low levels of small dense LDL and high levels of large buoyant HDL in the HVs as well as high levels of large buoyant LDL and total HDL in patients with MS. We conclude that the presence of MS weakens or abolishes the strong associations between adiponectin and the lipoprotein parameters observed in HVs and disturbs the complex interplay between adiponectin and lipoprotein metabolism.
Collapse
Affiliation(s)
- Iva Klobučar
- Department of Cardiology, Sisters of Charity University Hospital Centre, 10000 Zagreb, Croatia; (I.K.); (M.T.)
| | - Hansjörg Habisch
- Otto Loewi Research Center, Medicinal Chemistry, Medical University of Graz, 8010 Graz, Austria; (H.H.); (T.M.)
| | - Lucija Klobučar
- Department of Medicine, University Hospital Centre Osijek, 31000 Osijek, Croatia;
| | - Matias Trbušić
- Department of Cardiology, Sisters of Charity University Hospital Centre, 10000 Zagreb, Croatia; (I.K.); (M.T.)
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia;
| | - Gudrun Pregartner
- Institute for Medical Informatics, Statistics, and Documentation, Medical University of Graz, 8036 Graz, Austria; (G.P.); (A.B.)
| | - Andrea Berghold
- Institute for Medical Informatics, Statistics, and Documentation, Medical University of Graz, 8036 Graz, Austria; (G.P.); (A.B.)
| | - Gerhard M. Kostner
- Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria;
| | - Hubert Scharnagl
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8036 Graz, Austria;
| | - Tobias Madl
- Otto Loewi Research Center, Medicinal Chemistry, Medical University of Graz, 8010 Graz, Austria; (H.H.); (T.M.)
- BioTechMed-Graz, 8010 Graz, Austria
| | - Saša Frank
- Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria;
- BioTechMed-Graz, 8010 Graz, Austria
| | - Vesna Degoricija
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia;
- Department of Medicine, Sisters of Charity University Hospital Centre, 10000 Zagreb, Croatia
| |
Collapse
|
|
12
|
Cho S, Dadson K, Sung HK, Ayansola O, Mirzaesmaeili A, Noskovicova N, Zhao Y, Cheung K, Radisic M, Hinz B, Sater AAA, Hsu HH, Lopaschuk GD, Sweeney G. Cardioprotection by the adiponectin receptor agonist ALY688 in a preclinical mouse model of heart failure with reduced ejection fraction (HFrEF). Biomed Pharmacother 2024; 171:116119. [PMID: 38181714 DOI: 10.1016/j.biopha.2023.116119] [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: 10/29/2023] [Revised: 12/28/2023] [Accepted: 12/29/2023] [Indexed: 01/07/2024] Open
Abstract
AIMS Adiponectin has been shown to mediate cardioprotective effects and levels are typically reduced in patients with cardiometabolic disease. Hence, there has been intense interest in developing adiponectin-based therapeutics. The aim of this translational research study was to examine the functional significance of targeting adiponectin signaling with the adiponectin receptor agonist ALY688 in a mouse model of heart failure with reduced ejection fraction (HFrEF), and the mechanisms of cardiac remodeling leading to cardioprotection. METHODS AND RESULTS Wild-type mice were subjected to transverse aortic constriction (TAC) to induce left ventricular pressure overload (PO), or sham surgery, with or without daily subcutaneous ALY688-SR administration. Temporal analysis of cardiac function was conducted via weekly echocardiography for 5 weeks and we observed that ALY688 attenuated the PO-induced dysfunction. ALY688 also reduced cardiac hypertrophic remodeling, assessed via LV mass, heart weight to body weight ratio, cardiomyocyte cross sectional area, ANP and BNP levels. ALY688 also attenuated PO-induced changes in myosin light and heavy chain expression. Collagen content and myofibroblast profile indicated that fibrosis was attenuated by ALY688 with TIMP1 and scleraxis/periostin identified as potential mechanistic contributors. ALY688 reduced PO-induced elevation in circulating cytokines including IL-5, IL-13 and IL-17, and the chemoattractants MCP-1, MIP-1β, MIP-1alpha and MIP-3α. Assessment of myocardial transcript levels indicated that ALY688 suppressed PO-induced elevations in IL-6, TLR-4 and IL-1β, collectively indicating anti-inflammatory effects. Targeted metabolomic profiling indicated that ALY688 increased fatty acid mobilization and oxidation, increased betaine and putrescine plus decreased sphingomyelin and lysophospholipids, a profile indicative of improved insulin sensitivity. CONCLUSION These results indicate that the adiponectin mimetic peptide ALY688 reduced PO-induced fibrosis, hypertrophy, inflammation and metabolic dysfunction and represents a promising therapeutic approach for treating HFrEF in a clinical setting.
Collapse
Affiliation(s)
- Sungji Cho
- Department of Biology, York University, Toronto, ON, Canada
| | - Keith Dadson
- Department of Biology, York University, Toronto, ON, Canada
| | | | | | - Ali Mirzaesmaeili
- School of Kinesiology and Health Science, York University, Toronto, ON, Canada
| | - Nina Noskovicova
- Faculty of Dentistry, University of Toronto, Toronto, ON M5S3E2, Canada
| | - Yimu Zhao
- Toronto General Hospital Research Institute, Toronto, ON M5G 2C4, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada
| | - Krisco Cheung
- Department of Chemical Engineering and Applied Chemistry; University of Toronto, Toronto, ON M5S 3E5, Canada
| | - Milica Radisic
- Toronto General Hospital Research Institute, Toronto, ON M5G 2C4, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada; Department of Chemical Engineering and Applied Chemistry; University of Toronto, Toronto, ON M5S 3E5, Canada
| | - Boris Hinz
- Faculty of Dentistry, University of Toronto, Toronto, ON M5S3E2, Canada; Laboratory of Tissue Repair and Regeneration, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON M5B 1T8, Canada
| | - Ali A Abdul Sater
- School of Kinesiology and Health Science, York University, Toronto, ON, Canada
| | - Henry H Hsu
- Allysta Pharmaceuticals Inc. Bellevue, WA, USA
| | - Gary D Lopaschuk
- Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
| | - Gary Sweeney
- Department of Biology, York University, Toronto, ON, Canada.
| |
Collapse
|
|
13
|
Engin A. Adiponectin Resistance in Obesity: Adiponectin Leptin/Insulin Interaction. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1460:431-462. [PMID: 39287861 DOI: 10.1007/978-3-031-63657-8_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
The adiponectin (APN) levels in obesity are negatively correlated with chronic subclinical inflammation markers. The hypertrophic adipocytes cause obesity-linked insulin resistance and metabolic syndrome. Furthermore, macrophage polarization is a key determinant regulating adiponectin receptor (AdipoR1/R2) expression and differential adiponectin-mediated macrophage inflammatory responses in obese individuals. In addition to decrease in adiponectin concentrations, the decline in AdipoR1/R2 messenger ribonucleic acid (mRNA) expression leads to a decrement in adiponectin binding to cell membrane, and this turns into attenuation in the adiponectin effects. This is defined as APN resistance, and it is linked with insulin resistance in high-fat diet-fed subjects. The insulin-resistant group has a significantly higher leptin-to-APN ratio. The leptin-to-APN ratio is more than twofold higher in obese individuals. An increase in expression of AdipoRs restores insulin sensitivity and β-oxidation of fatty acids via triggering intracellular signal cascades. The ratio of high molecular weight to total APN is defined as the APN sensitivity index (ASI). This index is correlated to insulin sensitivity. Homeostasis model of assessment (HOMA)-APN and HOMA-estimated insulin resistance (HOMA-IR) are the most suitable methods to estimate the metabolic risk in metabolic syndrome. While morbidly obese patients display a significantly higher plasma leptin and soluble (s)E-selectin concentrations, leptin-to-APN ratio, there is a significant negative correlation between leptin-to-APN ratio and sP-selectin in obese patients. When comparing the metabolic dysregulated obese group with the metabolically healthy obese group, postprandial triglyceride clearance, insulin resistance, and leptin resistance are significantly delayed following the oral fat tolerance test in the first group. A neuropeptide, Spexin (SPX), is positively correlated with the quantitative insulin sensitivity check index (QUICKI) and APN. APN resistance together with insulin resistance forms a vicious cycle. Despite normal or high APN levels, an impaired post-receptor signaling due to adaptor protein-containing pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif 1 (APPL1)/APPL2 may alter APN efficiency and activity. However, APPL2 blocks adiponectin signaling through AdipoR1 and AdipoR2 because of the competitive inhibition of APPL1. APPL1, the intracellular binding partner of AdipoRs, is also an important mediator of adiponectin-dependent insulin sensitization. The elevated adiponectin levels with adiponectin resistance are compensatory responses in the condition of an unusual discordance between insulin resistance and APN unresponsiveness. Hypothalamic recombinant adeno-associated virus (rAAV)-leptin (Lep) gene therapy reduces serum APN levels, and it is a more efficient strategy for long-term weight maintenance.
Collapse
Affiliation(s)
- Atilla Engin
- Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, Ankara, Turkey.
- Mustafa Kemal Mah. 2137. Sok. 8/14, 06520, Cankaya, Ankara, Turkey.
| |
Collapse
|
|
14
|
Al Zein M, Zein O, Diab R, Dimachkie L, Sahebkar A, Al-Asmakh M, Kobeissy F, Eid AH. Intermittent fasting favorably modulates adipokines and potentially attenuates atherosclerosis. Biochem Pharmacol 2023; 218:115876. [PMID: 37871879 DOI: 10.1016/j.bcp.2023.115876] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/19/2023] [Accepted: 10/20/2023] [Indexed: 10/25/2023]
Abstract
Adipose tissue is now recognized as an endocrine organ that secretes bioactive molecules called adipokines. These biomolecules regulate key physiological functions, including insulin sensitivity, energy metabolism, appetite regulation, endothelial function and immunity. Dysregulated secretion of adipokines is intimately associated with obesity, and translates into increased risk of obesity-related cardiovasculo-metabolic diseases. In particular, emerging evidence suggests that adipokine imbalance contributes to the pathogenesis of atherosclerosis. One of the promising diet regimens that is beneficial in the fight against obesity and cardiometabolic disorders is intermittent fasting (IF). Indeed, IF robustly suppresses inflammation, meditates weight loss and mitigates many aspects of the cardiometabolic syndrome. In this paper, we review the main adipokines and their role in atherosclerosis, which remains a major contributor to cardiovascular-associated morbidity and mortality. We further discuss how IF can be employed as an effective management modality for obesity-associated atherosclerosis. By exploring a plethora of the beneficial effects of IF, particularly on inflammatory markers, we present IF as a possible intervention to help prevent atherosclerosis.
Collapse
Affiliation(s)
- Mohammad Al Zein
- Faculty of Medical Sciences, Lebanese University, Hadath, Beirut, Lebanon
| | - Omar Zein
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Rawan Diab
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Lina Dimachkie
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maha Al-Asmakh
- Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, Doha, Qatar; Biomedical Research Center, Qatar University, Doha, Qatar
| | - Firas Kobeissy
- Department of Neurobiology and Neuroscience, Morehouse School of Medicine, Atlanta, GA, USA
| | - Ali H Eid
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar.
| |
Collapse
|
|
15
|
Aisike G, Kuerbanjiang M, Muheyati D, Zaibibuli K, Lv MX, Han J. Correlation analysis of obesity phenotypes with leptin and adiponectin. Sci Rep 2023; 13:17718. [PMID: 37853077 PMCID: PMC10584881 DOI: 10.1038/s41598-023-43550-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 09/25/2023] [Indexed: 10/20/2023] Open
Abstract
Obesity can be categorized as metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). However, individuals with MHO are characterized by the absence of metabolic syndrome (MS) and appear to have lower inflammation levels compared to MUO. This study aimed to investigate the association of obesity phenotypes with leptin (LEP) and adiponectin (ADP). According to the inclusion and exclusion criteria, we selected 178 subjects from the previous cross-sectional survey. Based on the body mass index (BMI) and diagnostic criteria of MS, we divided the individuals into three groups, including healthy control group (HC group), metabolically healthy obesity group (MHO group) and metabolically unhealthy obesity group (MUO group). The concentrations of LEP and ADP in serum were measured, and the association of these two cytokines with different obesity phenotypes were subsequently analyzed. Compared to both the HC and MHO groups, the MUO group showed significantly higher BMI, waist circumference (WC), waist-hip ratio (WHR), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (Homa-IR) and blood pressure (P < 0.05). In contrast, serum high-density lipoprotein cholesterol (HDL-C) was notably lower in the MUO group (P < 0.05). ADP was found to have a positive correlation with systolic blood pressure (SBP) and a negative correlation with FPG in the MHO group. In the MUO group, LEP demonstrated a positive correlation with fasting insulin (FINS) and Homa-IR, while ADP showed a positive correlation with TC and SBP. Linear regression analysis further indicated that SBP (β = 0.234, P = 0.043), TG (β = - 0.292, P = 0.001) and LDL-C (β = 0.626, P = 0.000) were independently correlated with ADP, and BMI (β = 0.398, P = 0.002) was independently correlated with LEP in obese individuals. In conclusion, ADP and LEP were closely related with glucose and lipid metabolism in obese individuals, these two cytokines might play critical roles in obesity-associated metabolic disorders.
Collapse
Affiliation(s)
- Guliqiekeran Aisike
- Department of Nutrition and Food Hygiene, College of Public Health, Xinjiang Medical University, Urumqi, 830011, China
| | - Maierheba Kuerbanjiang
- Department of Nutrition and Food Hygiene, College of Public Health, Xinjiang Medical University, Urumqi, 830011, China
| | - Dina Muheyati
- Department of Nutrition and Food Hygiene, College of Public Health, Xinjiang Medical University, Urumqi, 830011, China
| | - Kaibinuer Zaibibuli
- Department of Nutrition and Food Hygiene, College of Public Health, Xinjiang Medical University, Urumqi, 830011, China
| | - Mei-Xia Lv
- Department of Nutrition and Food Hygiene, College of Public Health, Xinjiang Medical University, Urumqi, 830011, China
| | - Jia Han
- Department of Nutrition and Food Hygiene, College of Public Health, Xinjiang Medical University, Urumqi, 830011, China.
| |
Collapse
|
|
16
|
Merzah MH, Diajil AR. Serum and salivary adiponectin levels as predictive markers for diabetes mellitus in children with a family history of diabetes. J Med Life 2023; 16:1561-1565. [PMID: 38313182 PMCID: PMC10835556 DOI: 10.25122/jml-2023-0023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 05/15/2023] [Indexed: 02/06/2024] Open
Abstract
Diabetes mellitus (DM) is a chronic, metabolic condition marked by defects in insulin production, action, or both. Environmental and genetic factors can contribute to the onset of diabetes mellitus. Adiponectin, a hormone affecting pancreatic beta cell proliferation, has emerged as a potential indicator of diabetes risk. This cross-sectional study aimed to evaluate serum and salivary adiponectin levels as predictors of diabetes mellitus in children with/without a family history of diabetes mellitus. The study was conducted at Al-Zahra Hospital in Najaf city and included 125 children aged 5 to 16. Data on demographics, including name, age, and gender, were collected, and body mass index (BMI) was assessed. Serum and salivary adiponectin levels were measured and analyzed in relation to family history and BMI. Children with a family history of DM had high serum adiponectin (ADP) levels. Serum adiponectin levels were significantly higher in children with first-degree relatives having a history of diabetes mellitus, except for cases involving mothers and other relatives with diabetes mellitus history (p<0.05). Furthermore, serum adiponectin levels were higher in obese children. Salivary adiponectin levels were significantly elevated in children with a maternal family history of diabetes (p=0.01), while no significant correlation was found with BMI. A significant negative correlation (r=-0.180, p=0.05) between salivary and serum adiponectin concentrations was observed. Compared to children with a normal, healthy weight, children with obesity had decreased salivary adiponectin levels and increased serum adiponectin levels.
Collapse
Affiliation(s)
- Maryam Hamid Merzah
- Department of Oral Diagnosis, Oral Medicine, College of Dentistry, University of Baghdad, Baghdad, Iraq
| | - Ameena Ryhan Diajil
- Department of Oral Diagnosis, Oral Medicine, College of Dentistry, University of Baghdad, Baghdad, Iraq
| |
Collapse
|
|
17
|
Amariuta T, Siewert-Rocks K, Price AL. Modeling tissue co-regulation estimates tissue-specific contributions to disease. Nat Genet 2023; 55:1503-1511. [PMID: 37580597 PMCID: PMC10904330 DOI: 10.1038/s41588-023-01474-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 07/13/2023] [Indexed: 08/16/2023]
Abstract
Integrative analyses of genome-wide association studies and gene expression data have implicated many disease-critical tissues. However, co-regulation of genetic effects on gene expression across tissues impedes distinguishing biologically causal tissues from tagging tissues. In the present study, we introduce tissue co-regulation score regression (TCSC), which disentangles causal tissues from tagging tissues by regressing gene-disease association statistics (from transcriptome-wide association studies) on tissue co-regulation scores, reflecting correlations of predicted gene expression across genes and tissues. We applied TCSC to 78 diseases/traits (average n = 302,000) and gene expression prediction models for 48 GTEx tissues. TCSC identified 21 causal tissue-trait pairs at a 5% false discovery rate (FDR), including well-established findings, biologically plausible new findings (for example, aorta artery and glaucoma) and increased specificity of known tissue-trait associations (for example, subcutaneous adipose, but not visceral adipose, and high-density lipoprotein). TCSC also identified 17 causal tissue-trait covariance pairs at 5% FDR. In conclusion, TCSC is a precise method for distinguishing causal tissues from tagging tissues.
Collapse
Affiliation(s)
- Tiffany Amariuta
- Halıcıoğlu Data Science Institute, University of California San Diego, La Jolla, CA, USA.
- Department of Medicine, University of California San Diego, La Jolla, CA, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
| | - Katherine Siewert-Rocks
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Alkes L Price
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
| |
Collapse
|
|
18
|
Lim JY, Kim E. The Role of Organokines in Obesity and Type 2 Diabetes and Their Functions as Molecular Transducers of Nutrition and Exercise. Metabolites 2023; 13:979. [PMID: 37755259 PMCID: PMC10537761 DOI: 10.3390/metabo13090979] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 08/22/2023] [Accepted: 08/24/2023] [Indexed: 09/28/2023] Open
Abstract
Maintaining systemic homeostasis requires the coordination of different organs and tissues in the body. Our bodies rely on complex inter-organ communications to adapt to perturbations or changes in metabolic homeostasis. Consequently, the liver, muscle, and adipose tissues produce and secrete specific organokines such as hepatokines, myokines, and adipokines in response to nutritional and environmental stimuli. Emerging evidence suggests that dysregulation of the interplay of organokines between organs is associated with the pathophysiology of obesity and type 2 diabetes (T2D). Strategies aimed at remodeling organokines may be effective therapeutic interventions. Diet modification and exercise have been established as the first-line therapeutic intervention to prevent or treat metabolic diseases. This review summarizes the current knowledge on organokines secreted by the liver, muscle, and adipose tissues in obesity and T2D. Additionally, we highlighted the effects of diet/nutrition and exercise on the remodeling of organokines in obesity and T2D. Specifically, we investigated the ameliorative effects of caloric restriction, selective nutrients including ω3 PUFAs, selenium, vitamins, and metabolites of vitamins, and acute/chronic exercise on the dysregulation of organokines in obesity and T2D. Finally, this study dissected the underlying molecular mechanisms by which nutrition and exercise regulate the expression and secretion of organokines in specific tissues.
Collapse
Affiliation(s)
- Ji Ye Lim
- Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), 6431 Fannin St., Houston, TX 77030, USA
| | - Eunju Kim
- Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), 6431 Fannin St., Houston, TX 77030, USA
| |
Collapse
|
|
19
|
Kaburagi T, Otsuka Y, Oshiro S. Antiobesity Effect of N-Acetylneuraminic Acid by Enhancing Antioxidative Capacity in Mice Fed a High-Fat Diet. J Med Food 2023; 26:550-559. [PMID: 37335945 DOI: 10.1089/jmf.2023.k.0016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/21/2023] Open
Abstract
The sialic acid N-acetylneuraminic acid (NANA), an essential factor in bioregulation, is a functional food component that is known to have beneficial health effects, but its antiobesity effect has not been clearly understood. Adipocyte dysfunction in obesity involves a decrease in the level of NANA sialylation. In this study, we investigated the antiobesity effect of NANA in mice fed a high-fat diet (HFD) and in 3T3-L1 adipocytes. Male C57BL/6J mice were randomly divided into three groups and administered the following diets: a normal diet, an HFD, and an HFD with 1% NANA supplementation for 12 weeks. NANA supplementation significantly reduced body weight gain; epididymal adipose tissue hypertrophy; and serum lipid, fasting glucose, and aspartate transaminase levels compared with those in HFD mice. The percentage of lipid droplets in hepatic tissue was also decreased by NANA supplementation in HFD mice. The downregulation of Adipoq expression and upregulation of Fabp4 expression induced by HFD in epididymal adipocytes were improved by NANA supplementation. The downregulation of Sod1 expression and increase in malondialdehyde level were induced by HFD, and they were significantly improved in the liver by NANA supplementation, but not in epididymal adipocytes. However, NANA supplementation had no effect on sialylation and antioxidant enzyme levels in mouse epididymal adipocytes and 3T3-L1 adipocytes. Overall, NANA exerts antiobesity and antihypolipidemic effects and may be beneficial in suppressing obesity-related diseases.
Collapse
Affiliation(s)
- Tomoko Kaburagi
- Department of Health Science, Daito Bunka University, Saitama, Japan
- Graduate School of Sports and Health Science, Division of Nutritional Physiology, Daito Bunka University, Saitama, Japan
| | - Yuko Otsuka
- Department of Health Science, Daito Bunka University, Saitama, Japan
| | - Satoru Oshiro
- Department of Health Science, Daito Bunka University, Saitama, Japan
- Graduate School of Sports and Health Science, Division of Nutritional Physiology, Daito Bunka University, Saitama, Japan
| |
Collapse
|
|
20
|
Mehri K, Hamidian G, Zavvari Oskuye Z, Nayebirad S, Farajdokht F. The role of apelinergic system in metabolism and reproductive system in normal and pathological conditions: an overview. Front Endocrinol (Lausanne) 2023; 14:1193150. [PMID: 37424869 PMCID: PMC10324965 DOI: 10.3389/fendo.2023.1193150] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 06/06/2023] [Indexed: 07/11/2023] Open
Abstract
Lifestyle changes have made metabolic disorders as one of the major threats to life. Growing evidence demonstrates that obesity and diabetes disrupt the reproductive system by affecting the gonads and the hypothalamus-pituitary-gonadal (HPG) axis. Apelin, an adipocytokine, and its receptor (APJ) are broadly expressed in the hypothalamus nuclei, such as paraventricular and supraoptic, where gonadotropin-releasing hormone (GnRH) is released, and all three lobes of the pituitary, indicating that apelin is involved in the control of reproductive function. Moreover, apelin affects food intake, insulin sensitivity, fluid homeostasis, and glucose and lipid metabolisms. This review outlined the physiological effects of the apelinergic system, the relationship between apelin and metabolic disorders such as diabetes and obesity, as well as the effect of apelin on the reproductive system in both gender. The apelin-APJ system can be considered a potential therapeutic target in the management of obesity-associated metabolic dysfunction and reproductive disorders.
Collapse
Affiliation(s)
- Keyvan Mehri
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Gholamreza Hamidian
- Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | | | - Sepehr Nayebirad
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Fereshteh Farajdokht
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|
|
21
|
Boutari C, Hill MA, Procaccini C, Matarese G, Mantzoros CS. The key role of inflammation in the pathogenesis and management of obesity and CVD. Metabolism 2023:155627. [PMID: 37302694 DOI: 10.1016/j.metabol.2023.155627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 06/06/2023] [Indexed: 06/13/2023]
Affiliation(s)
- Chrysoula Boutari
- Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki, Greece; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
| | - Michael A Hill
- Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO 65212, USA; Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, MO 65212, USA
| | - Claudio Procaccini
- Laboratorio di Immunologia, Istituto per l'Endocrinologia e l'Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), 80131 Naples, Italy; Unità di Neuroimmunologia, IRCCS-Fondazione Santa Lucia, 00143 Rome, Italy
| | - Giuseppe Matarese
- Laboratorio di Immunologia, Istituto per l'Endocrinologia e l'Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), 80131 Naples, Italy; Treg Cell Lab, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", 80131 Naples, Italy
| | - Christos S Mantzoros
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Medicine, Boston VA Healthcare System, Boston, MA, USA
| |
Collapse
|
|
22
|
Zu Y, Pahlavani M, Ramalingam L, Jayarathne S, Andrade J, Scoggin S, Festuccia WT, Kalupahana NS, Moustaid-Moussa N. Temperature-Dependent Effects of Eicosapentaenoic Acid (EPA) on Browning of Subcutaneous Adipose Tissue in UCP1 Knockout Male Mice. Int J Mol Sci 2023; 24:ijms24108708. [PMID: 37240054 DOI: 10.3390/ijms24108708] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 05/02/2023] [Accepted: 05/03/2023] [Indexed: 05/28/2023] Open
Abstract
Uncoupling protein 1 (UCP1) plays a central role in thermogenic tissues by uncoupling cellular respiration to dissipate energy. Beige adipocytes, an inducible form of thermogenic cells in subcutaneous adipose tissue (SAT), have become a major focus in obesity research. We have previously shown that eicosapentaenoic acid (EPA) ameliorated high-fat diet (HFD)-induced obesity by activating brown fat in C57BL/6J (B6) mice at thermoneutrality (30 °C), independently of UCP1. Here, we investigated whether ambient temperature (22 °C) impacts EPA effects on SAT browning in wild-type (WT) and UCP1 knockout (KO) male mice and dissected underlying mechanisms using a cell model. We observed resistance to diet-induced obesity in UCP1 KO mice fed HFD at ambient temperature, with significantly higher expression of UCP1-independent thermogenic markers, compared to WT mice. These markers included the fibroblast growth factor 21 (FGF21) and sarco/endoplasmic reticulum Ca2+-ATPase 2b (SERCA2b), suggesting the indispensable role of temperature in beige fat reprogramming. Surprisingly, although EPA induced thermogenic effects in SAT-derived adipocytes harvested from both KO and WT mice, EPA only increased thermogenic gene and protein expression in the SAT of UCP1 KO mice housed at ambient temperature. Collectively, our findings indicate that the thermogenic effects of EPA, which are independent of UCP1, occur in a temperature-dependent manner.
Collapse
Affiliation(s)
- Yujiao Zu
- Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA
- Obesity Research Institute, Texas Tech University, Lubbock, TX 79409, USA
| | - Mandana Pahlavani
- Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA
- Obesity Research Institute, Texas Tech University, Lubbock, TX 79409, USA
| | - Latha Ramalingam
- Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA
- Obesity Research Institute, Texas Tech University, Lubbock, TX 79409, USA
| | - Shasika Jayarathne
- Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA
- Obesity Research Institute, Texas Tech University, Lubbock, TX 79409, USA
| | - Jose Andrade
- Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA
- Obesity Research Institute, Texas Tech University, Lubbock, TX 79409, USA
| | - Shane Scoggin
- Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA
- Obesity Research Institute, Texas Tech University, Lubbock, TX 79409, USA
| | - William T Festuccia
- Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil
| | - Nishan S Kalupahana
- Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA
- Department of Physiology, Faculty of Medicine, University of Peradeniya, Peradeniya 20400, Sri Lanka
| | - Naima Moustaid-Moussa
- Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA
- Obesity Research Institute, Texas Tech University, Lubbock, TX 79409, USA
| |
Collapse
|
|
23
|
Masenga SK, Kabwe LS, Chakulya M, Kirabo A. Mechanisms of Oxidative Stress in Metabolic Syndrome. Int J Mol Sci 2023; 24:7898. [PMID: 37175603 PMCID: PMC10178199 DOI: 10.3390/ijms24097898] [Citation(s) in RCA: 179] [Impact Index Per Article: 89.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 04/24/2023] [Accepted: 04/25/2023] [Indexed: 05/15/2023] Open
Abstract
Metabolic syndrome is a cluster of conditions associated with the risk of diabetes mellitus type 2 and cardiovascular diseases (CVDs). Metabolic syndrome is closely related to obesity. Increased adiposity promotes inflammation and oxidative stress, which are precursors of various complications involving metabolic syndrome components, namely insulin resistance, hypertension, and hyperlipidemia. An increasing number of studies confirm the importance of oxidative stress and chronic inflammation in the etiology of metabolic syndrome. However, few studies have reviewed the mechanisms underlying the role of oxidative stress in contributing to metabolic syndrome. In this review, we highlight mechanisms by which reactive oxygen species (ROS) increase mitochondrial dysfunction, protein damage, lipid peroxidation, and impair antioxidant function in metabolic syndrome. Biomarkers of oxidative stress can be used in disease diagnosis and evaluation of severity.
Collapse
Affiliation(s)
- Sepiso K. Masenga
- HAND Research Group, School of Medicine and Health Sciences, Mulungushi University, Livingstone Campus, Livingstone P.O. Box 60009, Zambia
- Department of Medicine, Room 536 Robinson Research Building, Vanderbilt University Medical Centre, Nashville, TN 37232-6602, USA
| | - Lombe S. Kabwe
- HAND Research Group, School of Medicine and Health Sciences, Mulungushi University, Livingstone Campus, Livingstone P.O. Box 60009, Zambia
| | - Martin Chakulya
- HAND Research Group, School of Medicine and Health Sciences, Mulungushi University, Livingstone Campus, Livingstone P.O. Box 60009, Zambia
| | - Annet Kirabo
- Department of Medicine, Room 536 Robinson Research Building, Vanderbilt University Medical Centre, Nashville, TN 37232-6602, USA
| |
Collapse
|
|
24
|
Lee SH, Shin C, Ko YH, Lee MS, Park MH, Pae CU, Yoon HK, Han C. Plasminogen Activator Inhibitor-1: Potential Inflammatory Marker in Late-life Depression. CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE : THE OFFICIAL SCIENTIFIC JOURNAL OF THE KOREAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY 2023; 21:147-161. [PMID: 36700321 PMCID: PMC9889913 DOI: 10.9758/cpn.2023.21.1.147] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 10/26/2021] [Accepted: 10/27/2021] [Indexed: 01/27/2023]
Abstract
Objective Although several previous studies have examined the association between late-life depression and blood adipokine levels, a marker of chronic inflammation, no studies have comprehensively considered the effects of metabolic syndrome, which is known to affect blood adipokine levels. This study examined blood adipokine levels in geriatric depression after adjusting for the effects of metabolic syndrome. Methods Participants were selected from the Ansan Geriatric Study (depression group [n = 76] and control group [n = 76]). Blood concentrations of four adipokines (adiponectin, resistin, neutrophil-gelatinase-associated lipocalin [NGAL], and plasminogen activator inhibitor-1 [PAI-1]) were measured using immunoassays. The effects of blood adipokine concentration on the diagnosis of depression were analyzed using multivariate logistic regression to adjust for the effects of metabolic syndrome and potential confounding factors. Results When the effects of metabolic syndrome and potential confounding factors were adjusted, only PAI-1 could explain the diagnosis of depression among all the adipokines. The depression group showed a lower blood PAI-1 level than the control group. Adiponectin, resistin, and NGAL could not explain the diagnosis of depression when the effects of metabolic syndrome and potential confounding factors were adjusted. Conclusion This study suggests the possibility that the blood PAI-1 levels in clinically pathological late-life depression may show contrasting results to those with subclinical depressive symptoms. Additionally, considering that most previous studies have been conducted with pre-geriatric populations, the study suggests the possibility that geriatric depression may show inflammatory changes with patterns that are different from those of depression in the pre-geriatric population.
Collapse
Affiliation(s)
- Seung-Hoon Lee
- Department of Psychiatry, Veterans Health Service Medical Center, Seoul, Korea
| | - Cheolmin Shin
- Department of Psychiatry, Korea University College of Medicine, Seoul, Korea
| | - Young-Hoon Ko
- Department of Psychiatry, Korea University College of Medicine, Seoul, Korea
| | - Moon-Soo Lee
- Department of Psychiatry, Korea University College of Medicine, Seoul, Korea
| | - Moon Ho Park
- Department of Neurology, Korea University College of Medicine, Seoul, Korea
| | - Chi-Un Pae
- Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ho-Kyoung Yoon
- Department of Psychiatry, Korea University College of Medicine, Seoul, Korea
| | - Changsu Han
- Department of Psychiatry, Korea University College of Medicine, Seoul, Korea,Address for correspondence: Changsu Han Department of Psychiatry, Korea University Guro Hospital, Korea University College of Medicine, 148 Gurodong-ro, Guro-gu, Seoul 08308, Korea, E-mail: , ORCID: https://orcid.org/0000-0002-4021-8907
| |
Collapse
|
|
25
|
Dietary intervention with 2 different fat profiles; role of the rs822393 variant in metabolic parameter changes. NUTR HOSP 2023; 40:49-58. [PMID: 36602131 DOI: 10.20960/nh.04205] [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: 12/29/2022] Open
Abstract
Introduction Introduction: rs822393 is related to dietary intervention responses. The aim of our study was to analyze the metabolic effects of 2 hypocaloric diets with a different fat profile during 3 months according to the genetic variant rs822393. Methods: a population of 361 obese patients were randomly allocated to one of two diets; Diet P (enriched in polyunsaturated fatty acids) vs. Diet M (enriched in monounsaturated fatty acids). Adiposity and biochemical parameters were determined. rs822393 was assessed by real-time PCR, with a dominant model analysis (CC vs CT+TT). Results: genotype distribution was: 221 CC (61.2 %), 115 CT (31.9 %) and 25 TT (6.9 %). Basal and post-intervention HDL cholesterol, adiponectin levels and adiponectin/leptin ratio were lower in T-allele than non-T-allele carriers. After both diets, BMI, weight, fat mass, waist circumference, systolic blood pressure, insulin levels, HOMA-IR, leptin, total cholesterol and LDL-cholesterol improved significantly in both genotype groups. After Diet P, HDL-cholesterol (delta: 5.6 ± 1.1 mg/dl vs. 2.7 ± 0.9 mg/dl; p = 0.01), serum adiponectin (20.1 ± 2.9 ng/dl vs. 6.8 ± 3.0 ng/dl; p = 0.02) and adiponectin/leptin ratio (0.57 ± 0.1 units vs. 0.20 ± 0.08 units; p = 0.03) improved in non-T allele carriers. The same improvements were observed after Diet M: HDL-cholesterol (delta: 5.5 ± 0.8 mg/dl vs. 3.1 ± 0.9 mg/dl; p = 0.03), serum adiponectin (19.5 ± 2.9 ng/dl vs. 4.5 ± 2.8 ng/dl; p = 0.01), and adiponectin/leptin ratio (0.54 ± 0.1 units vs. 0.15 ± 0.08 units; p = 0.03). These parameters remained unchanged in T-allele carriers. Conclusion: after two different hypocaloric diets, obese subjects with the T allele of rs822393 did not improve their adiponectin levels, ratio adiponectin/leptin, and HDL-cholesterol, despite loss of weight.
Collapse
|
|
26
|
Rashidmayvan M, Sahebi R, Avan A, Sharifan P, Esmaily H, Afshari A, Nattagh-Eshtivani E, Najar Sedghdoust F, Aghasizadeh M, Ferns GA, Ghayour-Mobarhan M. Double blind control trial of vitamin D fortified milk on the expression of lncRNAs and adiponectin for patients with metabolic syndrome. Diabetol Metab Syndr 2023; 15:9. [PMID: 36653874 PMCID: PMC9847060 DOI: 10.1186/s13098-023-00979-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 01/05/2023] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Metabolic syndrome (Mets) is a common metabolic disorder in which hypoadiponectinemia is one of the consequences for the body caused by inflammation, and vitamin D may help improve inflammatory symptoms. LncRNAs (long non-coding RNA) play several different regulatory roles in the body. The goal of this study was to see how adding vitamin D to milk affected the levels of adiponectin and inflammatory lncRNAs in the serum of people with Mets. METHODS This clinical trial was conducted on staff and students between the ages of 30 and 50 at Mashhad University of Medical Sciences and met the International Diabetes Federation's criteria for Mets. Eighty-two Mets were assigned randomly to one of two groups for ten weeks: fortified milk (FM) with 1500 IU vitamin D or non-fortified milk (NFM). Total RNA was extracted from both frozen clinical samples using Trizol reagent. APQ AS and MALAT1 lncRNA gene expression were measured by Real-Time PCR. RESULTS Serum adiponectin levels in the FM group increased significantly compared to the NFM group (p = 0.01). Also, the expression of APQ AS and MALAT1 genes decreased after ten weeks, which showed a significant decrease in APQ AS (p = 0.036). CONCLUSION As in FM, vitamin D may have anti-inflammatory effects and increase adiponectin levels in people with Mets via decreasing APQ AS gene expression.
Collapse
Affiliation(s)
- Mohammad Rashidmayvan
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reza Sahebi
- Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Avan
- Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Payam Sharifan
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Habibollah Esmaily
- Department of Biostatistics, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Asma Afshari
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elyas Nattagh-Eshtivani
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fatemeh Najar Sedghdoust
- Iranian UNESCO Center of Excellence for Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Malihe Aghasizadeh
- Iranian UNESCO Center of Excellence for Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Division of Medical Education, Brighton & Sussex Medical School, Falmer, Brighton, Sussex, UK
| | - Majid Ghayour-Mobarhan
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
- Iranian UNESCO Center of Excellence for Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran.
| |
Collapse
|
|
27
|
Arlien-Søborg MC, Madsen MA, Dal J, Krusenstjerna-Hafstrøm T, Ringgaard S, Skou N, Høgild M, Jørgensen JOL. Ectopic lipid deposition and insulin resistance in patients with GH disorders before and after treatment. Eur J Endocrinol 2023; 188:6984866. [PMID: 36651164 DOI: 10.1093/ejendo/lvac014] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 12/02/2022] [Accepted: 12/08/2022] [Indexed: 01/13/2023]
Abstract
OBJECTIVES Insulin resistance is associated with ectopic lipid deposition. Growth hormone (GH) status also modulates ectopic lipid accumulation, but how this associates with insulin resistance in patients with GH disorders is not well established. DESIGN AND METHODS Twenty-one patients diagnosed with acromegaly and 12 patients with adult GH deficiency (GHD) were studied at diagnosis and after treatment. A reference group of 12 subjects was included. Each study day comprised assessment of body composition with dual-energy X-ray absorptiometry, ectopic lipid deposition in the liver by MR spectroscopy, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). RESULTS Disease control of acromegaly decreased lean body mass (LBM) (P < .000) and increased the percentage of total body fat (TBF) (P < .000). GH replacement increased LBM in the GHD patients (P = .007) and decreased the percentage of TBF (P = .010). The intrahepatic lipid (IHL) content increased after disease control in acromegaly (P = .004), whereas IHL did not change significantly after GH replacement in GHD (P = .34). Insulin resistance (HOMA-IR) improved after disease control of acromegaly (P < .000) and remained unaltered after GH replacement in the GHD patients (P = .829). CONCLUSIONS GH status is a significant modulator of body composition and insulin sensitivity.GH excess reduces total fat mass and intrahepatic lipid content together with induction of insulin resistance.The data support the notion that GH-induced insulin resistance is unassociated with hepatic lipid accumulation.
Collapse
Affiliation(s)
- Mai C Arlien-Søborg
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Medical Research Laboratory, Aarhus University Hospital, Aarhus, Denmark
| | - Michael Alle Madsen
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Aarhus, Denmark
| | - Jakob Dal
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark
| | | | - Steffen Ringgaard
- Department of Clinical Medicine, The MR Research Centre, Aarhus University Hospital, Aarhus, Denmark
| | - Nickolaj Skou
- Department of Radiology, Aarhus University Hospital, Aarhus, Denmark
| | - Morten Høgild
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Medical Research Laboratory, Aarhus University Hospital, Aarhus, Denmark
| | - Jens Otto Lunde Jørgensen
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Medical Research Laboratory, Aarhus University Hospital, Aarhus, Denmark
| |
Collapse
|
|
28
|
Hasbullah FY, Mohd Yusof BN, Abdul Ghani R, Mat Daud Z‘A, Appannah G, Abas F, Shyam S. Maternal and Dietary Factors Are Associated with Metabolic Syndrome in Women with a Previous History of Gestational Diabetes Mellitus. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:16797. [PMID: 36554678 PMCID: PMC9779785 DOI: 10.3390/ijerph192416797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 12/06/2022] [Accepted: 12/11/2022] [Indexed: 06/17/2023]
Abstract
While it is known that women with a previous history of gestational diabetes mellitus (post-GDM) have a higher risk of metabolic syndrome (MetS), evidence of lifestyle practices from low- and middle-income countries (LMICs) is still scarce. This study aimed to determine the factors associated with MetS in women post-GDM. This cross-sectional study involved 157 women post-GDM (mean age 34.8 ± 5.6 years) sampled from Selangor, Malaysia. We collected data on sociodemographic characteristics and obstetric history. Food intake was assessed using a food frequency questionnaire, and dietary patterns were derived from principal component analysis. MetS was diagnosed according to the 2009 Harmonized criteria. The prevalence of MetS in this study was 22.3%. Western dietary pattern consumption was correlated with MetS, body mass index (BMI), waist circumference, and triglyceride levels. Independent factors associated with MetS were lower education level (odds ratio, OR 4.017, p = 0.007), pre-pregnancy BMI (OR 1.192, p = 0.002), and Caesarean delivery (OR 3.798, p = 0.009). The study identified the maternal and dietary factors associated with MetS in women post-GDM in Malaysia. Community-based interventions that include dietary modification are warranted to prevent MetS and its complications, thus helping to reduce the overall disease burden.
Collapse
Affiliation(s)
- Farah Yasmin Hasbullah
- Department of Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
| | - Barakatun-Nisak Mohd Yusof
- Department of Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
- Diabetes Research Unit, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
- Institute for Social Science Studies, Putra Infoport, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
| | - Rohana Abdul Ghani
- Department of Internal Medicine, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor, Malaysia
| | - Zulfitri ‘Azuan Mat Daud
- Department of Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
| | - Geeta Appannah
- Department of Nutrition, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
| | - Faridah Abas
- Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
| | - Sangeetha Shyam
- Unitat de Nutrició Humana, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, 43201 Reus, Spain
- Institut d’Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari Sant Joan de Reus, 43204 Reus, Spain
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
- Centre for Translational Research, IMU Institute for Research and Development (IRDI), International Medical University (IMU), Kuala Lumpur 57000, Malaysia
| |
Collapse
|
|
29
|
Cho Y, Lee SY. Useful Biomarkers of Metabolic Syndrome. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:15003. [PMID: 36429722 PMCID: PMC9690835 DOI: 10.3390/ijerph192215003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 11/13/2022] [Indexed: 05/30/2023]
Abstract
The Special Issue call for papers on "Metabolic syndrome and its association with biomarkers" was proposed to present research on various markers for pathophysiology and the early detection of metabolic syndrome (MetS) [...].
Collapse
Affiliation(s)
- Younghye Cho
- Department of Family Medicine and Biomedical Research Institute, Yangsan Hospital, Pusan National University, Yangsan 50612, Republic of Korea
| | - Sang Yeoup Lee
- Department of Family Medicine and Biomedical Research Institute, Yangsan Hospital, Pusan National University, Yangsan 50612, Republic of Korea
- Department of Medical Education, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea
- Integrated Research Institute for Natural Ingredients and Functional Foods, Yangsan 50612, Republic of Korea
| |
Collapse
|
|
30
|
Effects of Irvingia gabonensis Extract on Metabolism, Antioxidants, Adipocytokines, Telomere Length, and Aerobic Capacity in Overweight/Obese Individuals. Nutrients 2022; 14:nu14214646. [PMID: 36364907 PMCID: PMC9656030 DOI: 10.3390/nu14214646] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 10/28/2022] [Accepted: 11/01/2022] [Indexed: 11/06/2022] Open
Abstract
We investigated the effects of Irvingia gabonensis (IG) kernel extract on the metabolism, adiposity indices, redox status, inflammation, adipocytokines, blood leukocyte relative telomere length (RTL), and aerobic capacity of overweight/obese individuals. All participants used the first 12-week phase to monitor body weight. They were then randomly divided into two groups: (1) 300 mg IG or (2) placebo (PLA). Both groups took one tablet per day for 12 weeks. The variables were measured before supplementation and after 3, 6, and 12 weeks of supplementation. RTL and aerobic capacity were measured before and after 12 weeks. Compared with the PLA, the IG increased plasma vitamin C after supplementation at 6 (p < 0.01) and 12 weeks (p < 0.05) and serum adiponectin after 3 weeks (p < 0.05). Compared with before supplementation, plasma malondialdehyde in the IG and serum leptin in the PLA were decreased after 12-week supplementation, without any differences between the groups. There were no differences between groups with respect to metabolism, inflammation, RTL, and aerobic capacity after the supplementation. We suggest that 12-week daily IG supplementation improved plasma vitamin C and adiponectin. The findings show the possible mechanism contributing to the effect of IG supplementation on a reduction in obesity-related complications.
Collapse
|
|
31
|
Zamboni M, Mazzali G, Brunelli A, Saatchi T, Urbani S, Giani A, Rossi AP, Zoico E, Fantin F. The Role of Crosstalk between Adipose Cells and Myocytes in the Pathogenesis of Sarcopenic Obesity in the Elderly. Cells 2022; 11:3361. [PMID: 36359757 PMCID: PMC9655977 DOI: 10.3390/cells11213361] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 10/08/2022] [Accepted: 10/14/2022] [Indexed: 11/15/2023] Open
Abstract
As a result of aging, body composition changes, with a decline in muscle mass and an increase in adipose tissue (AT), which reallocates from subcutaneous to visceral depots and stores ectopically in the liver, heart and muscles. Furthermore, with aging, muscle and AT, both of which have recognized endocrine activity, become dysfunctional and contribute, in the case of positive energy balance, to the development of sarcopenic obesity (SO). SO is defined as the co-existence of excess adiposity and low muscle mass and function, and its prevalence increases with age. SO is strongly associated with greater morbidity and mortality. The pathogenesis of SO is complex and multifactorial. This review focuses mainly on the role of crosstalk between age-related dysfunctional adipose and muscle cells as one of the mechanisms leading to SO. A better understanding of this mechanisms may be useful for development of prevention strategies and treatments aimed at reducing the occurrence of SO.
Collapse
Affiliation(s)
- Mauro Zamboni
- Geriatrics Division, Department of Surgery, Dentistry, Pediatric and Gynecology, Healthy Aging Center, University of Verona, 37126 Verona, Italy
| | - Gloria Mazzali
- Geriatrics Division, Department of Medicine, University of Verona, 37126 Verona, Italy
| | - Anna Brunelli
- Geriatrics Division, Department of Surgery, Dentistry, Pediatric and Gynecology, Healthy Aging Center, University of Verona, 37126 Verona, Italy
| | - Tanaz Saatchi
- Geriatrics Division, Department of Surgery, Dentistry, Pediatric and Gynecology, Healthy Aging Center, University of Verona, 37126 Verona, Italy
| | - Silvia Urbani
- Geriatrics Division, Department of Surgery, Dentistry, Pediatric and Gynecology, Healthy Aging Center, University of Verona, 37126 Verona, Italy
| | - Anna Giani
- Geriatrics Division, Department of Surgery, Dentistry, Pediatric and Gynecology, Healthy Aging Center, University of Verona, 37126 Verona, Italy
| | - Andrea P. Rossi
- Geriatrics Division, Department of Medicine, AULSS2, Ospedale Ca’Foncello, 31100 Treviso, Italy
| | - Elena Zoico
- Geriatrics Division, Department of Medicine, University of Verona, 37126 Verona, Italy
| | - Francesco Fantin
- Geriatrics Division, Department of Medicine, University of Verona, 37126 Verona, Italy
| |
Collapse
|
|
32
|
Tunçel ÖK, Altunkaynak Z, Bilgici B, Karaustaoğlu A, Gümrükçüoğlu Tİ. Increased growth hormone secretagogue receptor-1a (GHSR-1a) in hypothalamus during olanzapine treatment in rats. Psychoneuroendocrinology 2022; 144:105862. [PMID: 35835020 DOI: 10.1016/j.psyneuen.2022.105862] [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: 04/02/2021] [Revised: 01/07/2022] [Accepted: 07/05/2022] [Indexed: 11/24/2022]
Abstract
Weight gain is the one of the most important factors which increases global burden of psychiatric disorder. Second-generation antipsychotics, olanzapine (Olz) and valproic acid (Vpa) in particular, are held responsible for weight gain. However, it is still uncertain how these drugs cause this. Thus, the rats selected for the experiment were randomly divided into 3 groups. The 1st group received only 0.5 ml saline solution intraperitoneally (n = 20, control group); the second group was given 200 mg / kg Vpa intraperitoneally (n = 20, Vpa group) and 2 mg / kg Olz was given intraperitoneally to the 3rd group (n = 20, Olz group) between 8 and 10 am for 30 days. We examined serum leptin, adiponectin, resistin, TNF-α, IL-6, ghrelin level and, the amount of ghrelin secreting cells in the stomach and growth hormone secretagogue receptor-1a (GHSR-1a, ghrelin receptor) expression in the hypothalamus. The hypothalamic GHS-1a receptor index was significantly higher in the Olz group compared with the control group and Vpa group (p = 0.036 and p = 0.016 respectively). Ghrelin immune positive cell index in stomach was statistically significantly lower in the Vpa group compared with the control and Olz groups (p = 0.028 and p = 0.013 respectively) There was no difference between the groups in terms of serum leptin, resistin, IL-6 and ghrelin levels. In the Vpa group, a statistically significant increase was found in serum adiponectin level compared with both the control group and the Olz group (p = 0009 and p = 0024 respectively) and, significant decrease was found in serum TNF-α level compared to Olz group (p = 0007). In conclusion, we found that the main cause of weight gain in Olz use was the increase in the number of hypothalamic ghrelin receptors. Investigating the mechanism by which Olz increases the number of ghrelin receptors may help to develop effective treatment strategies in preventing obesity in psychiatric patients.
Collapse
Affiliation(s)
- Özgür Korhan Tunçel
- Medical Biochemistry Department, Faculty of Medicine, Ondokuz Mayıs University, 55139 Samsun, Turkey.
| | - Zuhal Altunkaynak
- Histology and Embryology Department, Faculty of Medicine, Ondokuz Mayıs University, 55139 Samsun, Turkey
| | - Birşen Bilgici
- Medical Biochemistry Department, Faculty of Medicine, Ondokuz Mayıs University, 55139 Samsun, Turkey
| | - Arzu Karaustaoğlu
- Medical Biochemistry Department, Faculty of Medicine, Ondokuz Mayıs University, 55139 Samsun, Turkey
| | - Taner İlker Gümrükçüoğlu
- Medical Biochemistry Department, Faculty of Medicine, Ondokuz Mayıs University, 55139 Samsun, Turkey
| |
Collapse
|
|
33
|
Girard D, Vandiedonck C. How dysregulation of the immune system promotes diabetes mellitus and cardiovascular risk complications. Front Cardiovasc Med 2022; 9:991716. [PMID: 36247456 PMCID: PMC9556991 DOI: 10.3389/fcvm.2022.991716] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 08/30/2022] [Indexed: 12/15/2022] Open
Abstract
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia due to insulin resistance or failure to produce insulin. Patients with DM develop microvascular complications that include chronic kidney disease and retinopathy, and macrovascular complications that mainly consist in an accelerated and more severe atherosclerosis compared to the general population, increasing the risk of cardiovascular (CV) events, such as stroke or myocardial infarction by 2- to 4-fold. DM is commonly associated with a low-grade chronic inflammation that is a known causal factor in its development and its complications. Moreover, it is now well-established that inflammation and immune cells play a major role in both atherosclerosis genesis and progression, as well as in CV event occurrence. In this review, after a brief presentation of DM physiopathology and its macrovascular complications, we will describe the immune system dysregulation present in patients with type 1 or type 2 diabetes and discuss its role in DM cardiovascular complications development. More specifically, we will review the metabolic changes and aberrant activation that occur in the immune cells driving the chronic inflammation through cytokine and chemokine secretion, thus promoting atherosclerosis onset and progression in a DM context. Finally, we will discuss how genetics and recent systemic approaches bring new insights into the mechanisms behind these inflammatory dysregulations and pave the way toward precision medicine.
Collapse
Affiliation(s)
- Diane Girard
- Université Paris Cité, INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker Enfants Malades, IMMEDIAB Laboratory, Paris, France
- Université Paris Cité, Institut Hors-Mur du Diabète, Faculté de Santé, Paris, France
| | - Claire Vandiedonck
- Université Paris Cité, INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker Enfants Malades, IMMEDIAB Laboratory, Paris, France
- Université Paris Cité, Institut Hors-Mur du Diabète, Faculté de Santé, Paris, France
| |
Collapse
|
|
34
|
Polymorphisms of the 11q23.3 Locus Affect the Risk and Mortality of Coronary Artery Disease. J Clin Med 2022; 11:jcm11154532. [PMID: 35956147 PMCID: PMC9369758 DOI: 10.3390/jcm11154532] [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] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 07/29/2022] [Accepted: 08/02/2022] [Indexed: 02/05/2023] Open
Abstract
Background: The present study aimed to determine whether the polymorphisms of the 11q23.3 locus affect the risk and mortality of coronary artery disease in 5-year and 10-year observations. Methods: The study group consisted of 519 subjects: 276 patients with CAD and 243 blood donors as controls. The genotyping of polymorphisms (rs10750097, rs3741298, and rs1729410) was performed using the TaqMan-PCR method. Survival was defined as the period from the angiographic confirmation of CAD to cardiovascular death, and the endpoint was defined as death from cardiovascular causes. Results: The G allele of the rs1729410 polymorphism increased the risk of CAD (OR = 1.55, p = 0.04) and showed a synergistic correlation with overweight/obesity (additive synergy index (SI) = 11.01, p < 0.001). The carriers of the GG genotype and over-normative LDL levels increased the risk of CAD by over 12-fold higher than expected (multiplicative synergy index (SIM) = 12.34, p < 0.001). In the case of the rs10750097 variant, an effect on mortality was shown in both 5-year and 10-year periods. Conclusion: The results revealed that the rs1729410 polymorphism increases the risk of CAD in synergy with traditional risk factors, and the rs10750097 polymorphism of the 11q23.3 locus affects the risk of death in patients with CAD.
Collapse
|
|
35
|
Kaza M, Tsentidis C, Vlachopapadopoulou E, Sakou II, Karanasios S, Mastorakos G, Karavanaki K. The Effect of Metabolic Profile on Leptin, Adiponectin, and hs-CRP in Children and Adolescents with Type 1 Diabetes. CHILDREN (BASEL, SWITZERLAND) 2022; 9:children9081162. [PMID: 36010052 PMCID: PMC9406437 DOI: 10.3390/children9081162] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Revised: 07/29/2022] [Accepted: 08/02/2022] [Indexed: 11/23/2022]
Abstract
Adipokines are a superfamily of cell signaling proteins produced by the adipose tissue. This study’s purpose was to reveal the association of adipokines (leptin, adiponectin), hs-CRP, and IL-6 with well-known cardiovascular risk factors (lipid profile, diabetes control, obesity, physical activity) in children and adolescents with T1D. This cross-sectional study included 80 participants (36 boys) with T1D, aged (mean ± SD) 14.8 ± 3.4 years. Body Mass Index (BMI), metabolic profile, and level of physical activity were assessed (using pedometers) for evaluation of their effect on serum leptin, adiponectin, IL-6, and hs-CRP. Leptin levels were associated with BMI (beta = 0.184, p < 0.001), waist to hip ratio (beta = −2.017, p = 0.022), Low Density Lipoprotein-C (LDL-C) (beta = 0.021, p = 0.005), and fat mass (beta = 14.07, p < 0.001). Adiponectin was correlated with waist to height ratio (beta = 0.048, p = 0.006), ΒΜΙ (beta = −0.056, p = 0.005), and muscle mass (beta = −0.013, p = 0.020). Interestingly, hs-CRP was associated with weight (beta = 0.035, p < 0.001), ΒΜI (beta = 0.186, p < 0.001), fat mass (beta = 5.2859, p = 0.004), and muscle mass (beta = 0.027, p = 0.008). Multiple regression analysis of muscle mass unveiled associations with log hs-CRP (beta = −1.237, p = 0.014) and inverse IL−6 (beta = 18.57, p = 0.01). Finally, multiple regression models of fat mass unveiled associations with physical activity (7-day-total-step-count) (beta = −3.90 × 10−7, p = 0.027), Inverse IL-6 (beta = −0.1572, p = 0.009), and squared leptin (beta = 0.0077, p = 0.03). This study reports a positive association of leptin with LDL-C, BMI, fat mass, and hip circumference and a negative association of adiponectin with BMI and muscle mass. Finally, hs-CRP was associated with HbA1c, fat mass, and BMI. We propose that leptin, adiponectin, and hs-CRP could be used as prognostic indicators of cardiovascular risk in children with T1D.
Collapse
Affiliation(s)
- Maria Kaza
- Diabetes and Metabolism Unit, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, “P&A Kyriakou” Children’s Hospital, 115 27 Athens, Greece; (I.-I.S.); (S.K.); (K.K.)
- Correspondence:
| | - Charalampos Tsentidis
- Department of Endocrinology, Metabolism & Diabetes Mellitus, General Hospital of Nikaia-Piraeus “Agios Panteleimon”, 184 54 Piraeus, Greece;
| | - Elpis Vlachopapadopoulou
- Department of Endocrinology Growth and Development, “P&A Kyriakou” Children’s Hospital, 115 27 Athens, Greece;
| | - Irine-Ikbale Sakou
- Diabetes and Metabolism Unit, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, “P&A Kyriakou” Children’s Hospital, 115 27 Athens, Greece; (I.-I.S.); (S.K.); (K.K.)
| | - Spyridon Karanasios
- Diabetes and Metabolism Unit, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, “P&A Kyriakou” Children’s Hospital, 115 27 Athens, Greece; (I.-I.S.); (S.K.); (K.K.)
| | - George Mastorakos
- Endocrine Unit, National and Kapodistrian University of Athens, “Aretaieion” Hospital, 115 28 Athens, Greece;
| | - Kyriaki Karavanaki
- Diabetes and Metabolism Unit, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, “P&A Kyriakou” Children’s Hospital, 115 27 Athens, Greece; (I.-I.S.); (S.K.); (K.K.)
| |
Collapse
|
|
36
|
Wada T, Yamamoto Y, Takasugi Y, Ishii H, Uchiyama T, Saitoh K, Suzuki M, Uchiyama M, Yoshitane H, Fukada Y, Shimba S. Adiponectin regulates the circadian rhythm of glucose and lipid metabolism. J Endocrinol 2022; 254:121-133. [PMID: 35662074 PMCID: PMC9354065 DOI: 10.1530/joe-22-0006] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 06/03/2022] [Indexed: 11/08/2022]
Abstract
Adiponectin is a cytokine secreted from adipocytes and regulates metabolism. Although serum adiponectin levels show diurnal variations, it is not clear if the effects of adiponectin are time-dependent. Therefore, this study conducted locomotor activity analyses and various metabolic studies using the adiponectin knockout (APN (-/-)) and the APN (+/+) mice to understand whether adiponectin regulates the circadian rhythm of glucose and lipid metabolism. We observed that the adiponectin gene deficiency does not affect the rhythmicity of core circadian clock genes expression in several peripheral tissues. In contrast, the adiponectin gene deficiency alters the circadian rhythms of liver and serum lipid levels and results in the loss of the time dependency of very-low-density lipoprotein-triglyceride secretion from the liver. In addition, the whole-body glucose tolerance of the APN (-/-) mice was normal at CT10 but reduced at CT22, compared to the APN (+/+) mice. The decreased glucose tolerance at CT22 was associated with insulin hyposecretion in vivo. In contrast, the gluconeogenesis activity was higher in the APN (-/-) mice than in the APN (+/+) mice throughout the day. These results indicate that adiponectin regulates part of the circadian rhythm of metabolism in the liver.
Collapse
Affiliation(s)
- Taira Wada
- Laboratory of Health Science, School of Pharmacy, Nihon University, Funabshi, Chiba, Japan
| | - Yukiko Yamamoto
- Laboratory of Health Science, School of Pharmacy, Nihon University, Funabshi, Chiba, Japan
| | - Yukiko Takasugi
- Laboratory of Health Science, School of Pharmacy, Nihon University, Funabshi, Chiba, Japan
| | - Hirotake Ishii
- Laboratory of Health Science, School of Pharmacy, Nihon University, Funabshi, Chiba, Japan
| | - Taketo Uchiyama
- Laboratory of Organic Chemistry, School of Pharmacy, Nihon University, Funabshi, Chiba, Japan
| | - Kaori Saitoh
- Department of Psychiatry, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
| | - Masahiro Suzuki
- Department of Psychiatry, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
| | - Makoto Uchiyama
- Department of Psychiatry, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
- Tokyo Adachi Hospital, Adachi, Tokyo, Japan
| | - Hikari Yoshitane
- Department of Biological Sciences, School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Yoshitaka Fukada
- Department of Biological Sciences, School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Shigeki Shimba
- Laboratory of Health Science, School of Pharmacy, Nihon University, Funabshi, Chiba, Japan
- Correspondence should be addressed to S Shimba:
| |
Collapse
|
|
37
|
Potential Therapeutic Agents That Target ATP Binding Cassette A1 (ABCA1) Gene Expression. Drugs 2022; 82:1055-1075. [PMID: 35861923 DOI: 10.1007/s40265-022-01743-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/20/2022] [Indexed: 11/03/2022]
Abstract
The cholesterol efflux protein ATP binding cassette protein A1 (ABCA) and apolipoprotein A1 (apo A1) are key constituents in the process of reverse-cholesterol transport (RCT), whereby excess cholesterol in the periphery is transported to the liver where it can be converted primarily to bile acids for either use in digestion or excreted. Due to their essential roles in RCT, numerous studies have been conducted in cells, mice, and humans to more thoroughly understand the pathways that regulate their expression and activity with the goal of developing therapeutics that enhance RCT to reduce the risk of cardiovascular disease. Many of the drugs and natural compounds examined target several transcription factors critical for ABCA1 expression in both macrophages and the liver. Likewise, several miRNAs target not only ABCA1 but also the same transcription factors that are critical for its high expression. However, after years of research and many preclinical and clinical trials, only a few leads have proven beneficial in this regard. In this review we discuss the various transcription factors that serve as drug targets for ABCA1 and provide an update on some important leads.
Collapse
|
|
38
|
Bhandari C, Agnihotr N. Pine nut oil supplementation alleviates the obesogenic effects in high-fat diet induced obese rats: A comparative study between epididymal and retroperitoneal adipose tissue. Nutr Res 2022; 106:85-100. [DOI: 10.1016/j.nutres.2022.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 07/19/2022] [Accepted: 07/24/2022] [Indexed: 11/24/2022]
|
|
39
|
Schmidt V, Hogan AE, Fallon PG, Schwartz C. Obesity-Mediated Immune Modulation: One Step Forward, (Th)2 Steps Back. Front Immunol 2022; 13:932893. [PMID: 35844529 PMCID: PMC9279727 DOI: 10.3389/fimmu.2022.932893] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 05/27/2022] [Indexed: 11/15/2022] Open
Abstract
Over the past decades, the relationship between the immune system and metabolism has become a major research focus. In this arena of immunometabolism the capacity of adipose tissue to secrete immunomodulatory molecules, including adipokines, within the underlying low-grade inflammation during obesity brought attention to the impact obesity has on the immune system. Adipokines, such as leptin and adiponectin, influence T cell differentiation into different T helper subsets and their activation during immune responses. Furthermore, within the cellular milieu of adipose tissue nutrient availability regulates differentiation and activation of T cells and changes in cellular metabolic pathways. Upon activation, T cells shift from oxidative phosphorylation to oxidative glycolysis, while the differential signaling of the kinase mammalian target of rapamycin (mTOR) and the nuclear receptor PPARγ, amongst others, drive the subsequent T cell differentiation. While the mechanisms leading to a shift from the typical type 2-dominated milieu in lean people to a Th1-biased pro-inflammatory environment during obesity are the subject of extensive research, insights on its impact on peripheral Th2-dominated immune responses become more evident. In this review, we will summarize recent findings of how Th2 cells are metabolically regulated during obesity and malnutrition, and how these states affect local and systemic Th2-biased immune responses.
Collapse
Affiliation(s)
- Viviane Schmidt
- Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany
| | - Andrew E. Hogan
- Kathleen Lonsdale Human Health Institute, Maynooth University, Maynooth, Ireland
- Obesity Immunology Research, St. Vincent’s University Hospital and University College Dublin, Dublin, Ireland
| | - Padraic G. Fallon
- Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Christian Schwartz
- Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany
- Medical Immunology Campus Erlangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany
- *Correspondence: Christian Schwartz,
| |
Collapse
|
|
40
|
Labusca L. Adipose tissue in bone regeneration - stem cell source and beyond. World J Stem Cells 2022; 14:372-392. [PMID: 35949397 PMCID: PMC9244952 DOI: 10.4252/wjsc.v14.i6.372] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Revised: 08/30/2021] [Accepted: 05/27/2022] [Indexed: 02/06/2023] Open
Abstract
Adipose tissue (AT) is recognized as a complex organ involved in major home-ostatic body functions, such as food intake, energy balance, immunomodulation, development and growth, and functioning of the reproductive organs. The role of AT in tissue and organ homeostasis, repair and regeneration is increasingly recognized. Different AT compartments (white AT, brown AT and bone marrow AT) and their interrelation with bone metabolism will be presented. AT-derived stem cell populations - adipose-derived mesenchymal stem cells and pluripotent-like stem cells. Multilineage differentiating stress-enduring and dedifferentiated fat cells can be obtained in relatively high quantities compared to other sources. Their role in different strategies of bone and fracture healing tissue engineering and cell therapy will be described. The current use of AT- or AT-derived stem cell populations for fracture healing and bone regenerative strategies will be presented, as well as major challenges in furthering bone regenerative strategies to clinical settings.
Collapse
Affiliation(s)
- Luminita Labusca
- Magnetic Materials and Sensors, National Institute of Research and Development for Technical Physics, Iasi 700050, Romania
- Orthopedics and Traumatology, County Emergency Hospital Saint Spiridon Iasi, Iasi 700050, Romania.
| |
Collapse
|
|
41
|
Queiroz-Glauss CP, Vieira MS, Gonçalves-Pereira MH, Almeida SS, Freire RH, Gomes MA, Alvarez-Leite JI, Santiago HC. Helminth infection modulates number and function of adipose tissue Tregs in high fat diet-induced obesity. PLoS Negl Trop Dis 2022; 16:e0010105. [PMID: 35499991 PMCID: PMC9098094 DOI: 10.1371/journal.pntd.0010105] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 05/12/2022] [Accepted: 04/01/2022] [Indexed: 11/23/2022] Open
Abstract
Background Epidemiological and experimental studies have shown a protective effect of helminth infections in weight gain and against the development of metabolic dysfunctions in the host. However, the mechanisms Treg cells exert in the helminth-obesity interface has been poorly investigated. The present study aimed to verify the influence of Heligmosomoides polygyrus infection in early stages of high fat diet-induced obesity. Principal findings The presence of infection was able to prevent exacerbated weight gain in mice fed with high fat diet when compared to non-infected controls. In addition, infected animals displayed improved insulin sensitivity and decreased fat accumulation in the liver. Obesity-associated inflammation was reduced in the presence of infection, demonstrated by lower levels of leptin and resistin, lower infiltration of Th1 and Th17 cells in adipose tissue, higher expression of IL10 and adiponectin, increased infiltration of Th2 and eosinophils in adipose tissue of infected animals. Of note, the parasite infection was associated with increased Treg frequency in adipose tissue which showed higher expression of cell surface markers of function and activation, like LAP and CD134. The infection could also increase adipose Treg suppressor function in animals on high fat diet. Conclusion These data suggest that H. polygyrus modulates adipose tissue Treg cells with implication for weight gain and metabolic syndrome. Helminth infections are known to modulate the immune system being responsible for protecting the host from developing allergic and autoimmune disorders (Hygiene Hypothesis). We hypothesized that the same immunomodulatory effect could have an impact on immunometabolic diseases, such as obesity and its linked diseases such as type 2 diabetes. Weight disorders have reached epidemic levels, nearly tripling since 1975 and being responsible for almost 5 million premature deaths each year, but have been spared in areas of high helminth prevalence. To test our hypothesis C57BL/6 male mice were fed control or high fat diet, for five weeks, in the presence or not of infection with the worm Heligmosomoides polygyrus. Weight gain, development of metabolic disorders, inflammation and cellular migration to the adipose tissue were evaluated. In accordance with our hypothesis, we found that the presence of infection prevented the exacerbated weight gain and also improved metabolic parameters in animals fed a high fat diet. This was associated with the infection’s ability to modulate parameters of a cell responsible for regulatory functions: Tregs. In the light of these findings, helminth infection could be protective against weight gain and metabolic disturbances.
Collapse
Affiliation(s)
- Camila P. Queiroz-Glauss
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Mariana S. Vieira
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Marcela Helena Gonçalves-Pereira
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Stephanie S. Almeida
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Rachel H. Freire
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Maria A. Gomes
- Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Jacqueline I. Alvarez-Leite
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Helton C. Santiago
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
- * E-mail:
| |
Collapse
|
|
42
|
Gomes-Pereira L, da Silva-Santos JE. Adipokines and Metabolic Syndrome: Pluripotent Markers for a Complex Relationship? Am J Hypertens 2022; 35:306-308. [PMID: 34849548 DOI: 10.1093/ajh/hpab184] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 11/25/2021] [Indexed: 11/13/2022] Open
Affiliation(s)
- Leonardo Gomes-Pereira
- Laboratory of Cardiovascular Biology, Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - José Eduardo da Silva-Santos
- Laboratory of Cardiovascular Biology, Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
| |
Collapse
|
|
43
|
Vichinsartvichai P, Teeramara R, Jirasawas T, Sakoonwatanyoo P. Comparison of urinary adiponectin in the presence of metabolic syndrome in peri- and postmenopausal women. BMC Womens Health 2022; 22:70. [PMID: 35287667 PMCID: PMC8919907 DOI: 10.1186/s12905-022-01655-8] [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: 09/29/2021] [Accepted: 03/09/2022] [Indexed: 11/11/2022] Open
Abstract
Objectives To find the association between urinary adiponectin and metabolic syndrome (MetS) in peri- and postmenopausal women and its potential application as a noninvasive screening for MetS. Methods A cross-sectional study was conducted in healthy peri- and postmenopausal women (defined by STRAW + 10 staging) aged at least 40 years who attended annual check-ups or menopause clinics were recruited. Baseline demographic data, MENQOL, anthropometric measurements, blood pressure, laboratory (FBS, total cholesterol, HDL-C, LDL-C, TG), and urinary adiponectin were collected. The MetS was diagnosed according to JIS 2009. Results 290 peri- and postmenopausal women had participated. The prevalence of Mets among our participants was 18%. Urinary adiponectin levels were similar in peri- and postmenopausal women with and without MetS (2.6 ± 2.2 vs. 2.3 ± 1.9 ng/mL, respectively, P = 0.55). Urinary adiponectin provides no diagnostic value for MetS (AUC = 0.516). Conclusions Urinary adiponectin has no role in screening and diagnosing MetS in peri- and postmenopausal women. The quest toward noninvasive screening for MetS is still going on.
Collapse
Affiliation(s)
- Patsama Vichinsartvichai
- Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, 681 Samsen Rd, Dusit, Bangkok, 10300, Thailand.
| | - Rattana Teeramara
- Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, 681 Samsen Rd, Dusit, Bangkok, 10300, Thailand
| | - Titima Jirasawas
- Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, 681 Samsen Rd, Dusit, Bangkok, 10300, Thailand
| | - Prirayapak Sakoonwatanyoo
- Department of Clinical Pathology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, 10300, Thailand
| |
Collapse
|
|
44
|
Plasminogen activator inhibitor-1 mediate downregulation of adiponectin in type 2 diabetes patients with metabolic syndrome. Cytokine X 2022; 4:100064. [PMID: 35128381 PMCID: PMC8803603 DOI: 10.1016/j.cytox.2022.100064] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 09/15/2021] [Accepted: 01/17/2022] [Indexed: 01/02/2023] Open
Abstract
Both Adiponectin and PAI-1 levels are associated with the Metabolic abnormalities. This study demonstrates that subjects with MetS have low adiponectin and higher PAI-1 levels compare to non-MetS. Higher PAI-1 levels are associated with higher odds of risk and prevalence of MetS. Pharmacological targeting of PAI-1 is necessary for MetS management. Introduction Metabolic syndrome (MetS) is a multifactorial disease characterized by metabolic abnormalities. Plasminogen activator inhibitor-1(PAI-1) is a key factor of the fibrinolysis its expression is elevated in insulin resistance, obesity, and MetS. In addition, an adiponectin produced by adipocytes is also key factor in MetS. This study aimed to investigate the relationship between PAI-1, adiponectin levels in MetS. Patients and Methods A total of 379 subjects were analyse in this cross-sectional study. MetS was defined by NCEP ATP-III criteria. Anthropometric, fasting blood glucose, HbA1c, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, PAI-1, and adiponectin were measured. Results PAI-1 levels were higher in MetS compared with non-MetS. In addition, adiponectin levels were significantly lower in MetS compared to non-MetS. Furthermore, increased level of PAI-1 corresponds with increase in prevalence of MetS. PAI-1 levels were significantly associated with MetS (OR = 2.51, CI = 1.23 – 5.14; p = 0.039). Conclusion PAI-1 increases the risk of MetS. PAI-1 and adiponectin regulation is useful in assesing the presence and severity of MetS. Further pharmacological targeting of PAI-1 studies are necessary for MetS management.
Collapse
|
|
45
|
Tagawa N, Fujinami A, Natsume S, Mizuno S, Kato I. Relationship between adiponectin multimer levels and subtypes of cerebral infarction. PLoS One 2022; 17:e0262542. [PMID: 35085298 PMCID: PMC8794129 DOI: 10.1371/journal.pone.0262542] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 12/28/2021] [Indexed: 01/08/2023] Open
Abstract
Aim Serum adiponectin levels are decreased in patients with cerebral infarction. Adiponectin in circulation exists in three isoforms: high molecular weight (HMW), medium molecular weight (MMW), and low molecular weight (LMW) adiponectin. We measured serum levels of total adiponectin and adiponectin multimers (HMW, MMW, and LMW) in patients with cerebral infarction and compared the serum levels of the three adiponectin multimers in stroke subtypes. We also evaluated the clinical value of adiponectin multimer levels as a biomarker for cerebral infarction. Methods We assessed a total of 132 patients with cerebral infarctions. The serum levels of total and adiponectin multimers were measured using enzyme-linked immunosorbent assay (ELISA). Results The total and HMW adiponectin levels were significantly lower in atherothrombotic infarction (AI) than in cerebral embolism (CE) (total, p < 0.05; HMW, p < 0.05). In male patients, the MMW adiponectin level was significantly lower in the lacunar infarction (LI) group than in the AI group (p < 0.05). The LMW adiponectin level was significantly lower in the AI group than in the LI and CE groups (LI, p < 0.001; CE, p = 0.001). However, there were no significant differences in adiponectin multimer levels among the stroke subtypes in female subjects. Additionally, in female patients with AI and LI, the LMW adiponectin levels were negatively associated with C-reactive protein (CRP; AI, p < 0.05; LI, p < 0.05). Conclusion These findings suggest that a decrease in adiponectin is associated with AI and that serum LMW adiponectin level represents a potential biomarker for AI.
Collapse
Affiliation(s)
- Noriko Tagawa
- Laboratory of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, Japan
| | - Aya Fujinami
- Comprehensive Education and Research Center, Kobe Pharmaceutical University, Kobe, Japan
| | | | - Shigeto Mizuno
- Endoscopy Department, Kindai University Nara Hospital, Ikoma, Japan
| | - Ikuo Kato
- Laboratory of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, Japan
- * E-mail:
| |
Collapse
|
|
46
|
Green tea extract increases adiponectin and PPARα levels to improve hepatic steatosis. J Nutr Biochem 2022; 103:108957. [DOI: 10.1016/j.jnutbio.2022.108957] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 11/18/2021] [Accepted: 01/05/2022] [Indexed: 01/08/2023]
|
|
47
|
Abstract
PURPOSE OF REVIEW The obesity epidemic is on the rise, and while it is well known that obesity is associated with an increase in cardiovascular risk factors such as type 2 diabetes mellitus, hypertension, and obstructive sleep apnea, recent data has highlighted that the degree and type of fat distribution may play a bigger role in the pathogenesis of cardiovascular disease (CVD) than body mass index (BMI) alone. We aim to review updated data on adipose tissue inflammation and distribution and CVD. RECENT FINDINGS We review the pathophysiology of inflammation secondary to adipose tissue, the association of obesity-related adipokines and CVD, and the differences and significance of brown versus white adipose tissue. We delve into the clinical manifestations of obesity-related inflammation in CVD. We discuss the available data on heterogeneity of adipose tissue-related inflammation with a focus on subcutaneous versus visceral adipose tissue, the differential pathophysiology, and clinical CVD manifestations of adipose tissue across sex, race, and ethnicity. Finally, we present the available data on lifestyle modification, medical, and surgical therapeutics on reduction of obesity-related inflammation. Obesity leads to a state of chronic inflammation which significantly increases the risk for CVD. More research is needed to develop non-invasive VAT quantification indices such as risk calculators which include variables such as sex, age, race, ethnicity, and VAT concentration, along with other well-known CVD risk factors in order to comprehensively determine risk of CVD in obese patients. Finally, pre-clinical biomarkers such as pro-inflammatory adipokines should be validated to estimate risk of CVD in obese patients.
Collapse
Affiliation(s)
- Mariam N Rana
- Department of Medicine, University Hospitals, 11100 Euclid Ave, Cleveland, OH, 44106, USA
| | - Ian J Neeland
- Department of Medicine, University Hospitals, 11100 Euclid Ave, Cleveland, OH, 44106, USA.
- Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
- Harrington Heart and Vascular Institute, University Hospitals, 11100 Euclid Ave, Cleveland, OH, 44106, USA.
| |
Collapse
|
|
48
|
Biomarkers in metabolic syndrome. Adv Clin Chem 2022; 111:101-156. [DOI: 10.1016/bs.acc.2022.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
|
|
49
|
Sibi JM, Mohan V, Deepa M, Babu S, Aravindhan V. Modulatory effect of filarial infection on the systemic hormone levels in subjects with metabolic syndrome (DM-LF5). Front Endocrinol (Lausanne) 2022; 13:1011942. [PMID: 36482987 PMCID: PMC9723321 DOI: 10.3389/fendo.2022.1011942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 11/01/2022] [Indexed: 11/23/2022] Open
Abstract
AIM Metabolic syndrome (MS) refers to a group of co-morbidities which include central obesity, hypertension, hyperglycemia and dyslipidemia. Previously, we reported that childhood lymphatic filariasis (LF) confers significant protection against type-1 and type-2 forms of diabetes, by means of immunomodulation. In the present study, we studied the effect of LF on endocrine dysfunction in MS and Non-MS patients in baseline and after 10 years of follow-up. METHODS We quantified the serum levels of pancreatic hormones (insulin and glucagon), incretins (Ghrelin, GIP and GLP-1) and adipokines (leptin, adiponectin, adipsin, visfatin, PAI-1 and resistin) by multiplex bead array system. RESULTS MS (both LF- and LF+) subjects had increased insulin levels compared to NMS (both LF- and LF+) subjects. MS-LF+ subjects had significantly increased levels of glucagon, ghrelin, GIP and GLP-1 and decreased levels of adipsin, compared to MS-LF- subjects. Interestingly this effect was short-lived and was not seen in the follow-up samples. CONCLUSION Overall, LF infection might confer limited short-term beneficial effects against MS, by means of modulating the incretin levels,either directly or indirectly.
Collapse
Affiliation(s)
- Joy Manohar Sibi
- Department of Genetics, Dr. A. L. Mudaliar Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai, India
| | - Viswanathan Mohan
- Madras Diabetes Research Foundation and Dr. Mohan’s Diabetes Specialties Centre, ICMR Center for Advanced Research on Diabetes and IDF Centre of Excellence in Diabetes Care, Chennai, India
| | - Mohan Deepa
- Madras Diabetes Research Foundation and Dr. Mohan’s Diabetes Specialties Centre, ICMR Center for Advanced Research on Diabetes and IDF Centre of Excellence in Diabetes Care, Chennai, India
| | - Subash Babu
- National Institute of Health-International Centre for Excellence in Research, National Institute for Research in Tuberculosis, Chennai, India
| | - Vivekanandhan Aravindhan
- Department of Genetics, Dr. A. L. Mudaliar Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai, India
- *Correspondence: Vivekanandhan Aravindhan,
| |
Collapse
|
|
50
|
Osimo EF, Sweeney M, de Marvao A, Berry A, Statton B, Perry BI, Pillinger T, Whitehurst T, Cook SA, O'Regan DP, Thomas EL, Howes OD. Adipose tissue dysfunction, inflammation, and insulin resistance: alternative pathways to cardiac remodelling in schizophrenia. A multimodal, case-control study. Transl Psychiatry 2021; 11:614. [PMID: 34873143 PMCID: PMC8648771 DOI: 10.1038/s41398-021-01741-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 11/17/2021] [Accepted: 11/23/2021] [Indexed: 12/12/2022] Open
Abstract
Cardiovascular diseases are the leading cause of death in schizophrenia. Patients with schizophrenia show evidence of concentric cardiac remodelling (CCR), defined as an increase in left-ventricular mass over end-diastolic volumes. CCR is a predictor of cardiac disease, but the molecular pathways leading to this in schizophrenia are unknown. We aimed to explore the relevance of hypertensive and non-hypertensive pathways to CCR and their potential molecular underpinnings in schizophrenia. In this multimodal case-control study, we collected cardiac and whole-body fat magnetic resonance imaging (MRI), clinical measures, and blood levels of several cardiometabolic biomarkers known to potentially cause CCR from individuals with schizophrenia, alongside healthy controls (HCs) matched for age, sex, ethnicity, and body surface area. Of the 50 participants, 34 (68%) were male. Participants with schizophrenia showed increases in cardiac concentricity (d = 0.71, 95% CI: 0.12, 1.30; p = 0.01), indicative of CCR, but showed no differences in overall content or regional distribution of adipose tissue compared to HCs. Despite the cardiac changes, participants with schizophrenia did not demonstrate activation of the hypertensive CCR pathway; however, they showed evidence of adipose dysfunction: adiponectin was reduced (d = -0.69, 95% CI: -1.28, -0.10; p = 0.02), with evidence of activation of downstream pathways, including hypertriglyceridemia, elevated C-reactive protein, fasting glucose, and alkaline phosphatase. In conclusion, people with schizophrenia showed adipose tissue dysfunction compared to body mass-matched HCs. The presence of non-hypertensive CCR and a dysmetabolic phenotype may contribute to excess cardiovascular risk in schizophrenia. If our results are confirmed, acting on this pathway could reduce cardiovascular risk and resultant life-years lost in people with schizophrenia.
Collapse
Affiliation(s)
- Emanuele F Osimo
- MRC London Institute of Medical Sciences and Imperial College London Institute of Clinical Sciences, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK. .,Department of Psychiatry, University of Cambridge, Cambridge, UK. .,Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK. .,South London and Maudsley NHS Foundation Trust, London, UK.
| | - Mark Sweeney
- MRC London Institute of Medical Sciences and Imperial College London Institute of Clinical Sciences, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.,Imperial College London, London, UK
| | - Antonio de Marvao
- MRC London Institute of Medical Sciences and Imperial College London Institute of Clinical Sciences, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK
| | - Alaine Berry
- MRC London Institute of Medical Sciences and Imperial College London Institute of Clinical Sciences, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK
| | - Ben Statton
- MRC London Institute of Medical Sciences and Imperial College London Institute of Clinical Sciences, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK
| | - Benjamin I Perry
- Department of Psychiatry, University of Cambridge, Cambridge, UK.,Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK
| | - Toby Pillinger
- MRC London Institute of Medical Sciences and Imperial College London Institute of Clinical Sciences, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.,South London and Maudsley NHS Foundation Trust, London, UK.,Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Thomas Whitehurst
- MRC London Institute of Medical Sciences and Imperial College London Institute of Clinical Sciences, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK
| | - Stuart A Cook
- MRC London Institute of Medical Sciences and Imperial College London Institute of Clinical Sciences, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK
| | - Declan P O'Regan
- MRC London Institute of Medical Sciences and Imperial College London Institute of Clinical Sciences, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK
| | - E Louise Thomas
- Research Centre for Optimal Health, School of Life Sciences, University of Westminster, London, UK
| | - Oliver D Howes
- MRC London Institute of Medical Sciences and Imperial College London Institute of Clinical Sciences, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK. .,South London and Maudsley NHS Foundation Trust, London, UK. .,Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
| |
Collapse
|