المؤلفون: Peter Strålfors, Belén Chanclón, Man Mohan Shrestha, Charlotta S. Olofsson, Cecilia Brännmark, Unn Kugelberg, Ingrid Wernstedt Asterholm, Emma I Kay

المصدر: Journal of Endocrinology. 247:25-38

مصطلحات موضوعية: Adult, 0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Adipocytes, White, Caveolin 1, Gene Expression, Adipose tissue, 030209 endocrinology & metabolism, Exocytosis, Mice, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Caveolae, medicine, Animals, Humans, Secretion, Adiponectin secretion, Obesity, Receptor, Aged, Mice, Knockout, Adiponectin, Chemistry, Cell Membrane, nutritional and metabolic diseases, Middle Aged, Diet, Mice, Inbred C57BL, 030104 developmental biology, Female, hormones, hormone substitutes, and hormone antagonists

الوصف: Here we have investigated the role of the protein caveolin 1 (Cav1) and caveolae in the secretion of the white adipocyte hormone adiponectin. Using mouse primary subcutaneous adipocytes genetically depleted of Cav1, we show that the adiponectin secretion, stimulated either adrenergically or by insulin, is abrogated while basal (unstimulated) release of adiponectin is elevated. Adiponectin secretion is similarly affected in wildtype mouse and human adipocytes where the caveolae structure was chemically disrupted. The altered ex vivo secretion in adipocytes isolated from Cav1 null mice is accompanied by lowered serum levels of the high-molecular weight (HMW) form of adiponectin, whereas the total concentration of adiponectin is unaltered. Interestingly, levels of HMW adiponectin are maintained in adipose tissue from Cav1-depleted mice, signifying that a secretory defect is present. The gene expression of key regulatory proteins known to be involved in cAMP/adrenergically triggered adiponectin exocytosis (the beta-3-adrenergic receptor and exchange protein directly activated by cAMP) remains intact in Cav1 null adipocytes. Microscopy and fractionation studies indicate that adiponectin vesicles do not co-localise with Cav1 but that some vesicles are associated with a specific fraction of caveolae. Our studies propose that Cav1 has an important role in secretion of HMW adiponectin, even though adiponectin-containing vesicles are not obviously associated with this protein. We suggest that Cav1, and/or the caveolae domain, is essential for the organisation of signalling pathways involved in the regulation of HMW adiponectin exocytosis, a function that is disrupted in Cav1/caveolae-depleted adipocytes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e0393efcc12e3b71a5bca878351111eTest
https://doi.org/10.1530/joe-20-0078Test

المؤلفون: Martin Adiels, Lena Björck, Soffia Gudbjörnsdottir, Araz Rawshani, Marcus Lind, Jon Edqvist, Ann-Marie Svensson, Naveed Sattar, Annika Rosengren

المصدر: Yearbook of Paediatric Endocrinology.

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Disease, Body Mass Index, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Thinness, Risk Factors, Weight loss, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Risk of mortality, Humans, Obesity, Registries, 030212 general & internal medicine, Aged, Sweden, Advanced and Specialized Nursing, Type 1 diabetes, Proportional hazards model, business.industry, Body Weight, Middle Aged, Prognosis, medicine.disease, Hospitalization, Diabetes Mellitus, Type 1, Cardiovascular Diseases, Female, medicine.symptom, business, Body mass index, Weight gain, Diabetic Angiopathies, Obesity paradox, Follow-Up Studies

الوصف: OBJECTIVE Low weight has been associated with increased mortality risks in type 1 diabetes. We aimed to investigate the importance of weight and weight gain/loss in the Swedish population diagnosed with type 1 diabetes. RESEARCH DESIGN AND METHODS Patients with type 1 diabetes (n = 26,125; mean age 33.3 years; 45% women) registered in the Swedish National Diabetes Registry from 1998 to 2012 were followed from the first day of study entry. Cox regression was used to calculate risk of death from cardiovascular disease (CVD), major CVD events, hospitalizations for heart failure (HF), and total deaths. RESULTS Population mean BMI in patients with type 1 diabetes increased from 24.7 to 25.7 kg/m2 from 1998 to 2012. Over a median follow-up of 10.9 years, there were 1,031 deaths (33.2% from CVD), 1,460 major CVD events, and 580 hospitalizations for HF. After exclusion of smokers, patients with poor metabolic control, and patients with a short follow-up time, there was no increased risk for mortality in those with BMI 25 kg/m2 was associated with a minor increase in risk of mortality, major CVD, and HF. In women, associations with BMI were largely absent. Weight gain implied an increased risk of mortality and HF, while weight loss was not associated with higher risk. CONCLUSIONS Risk of major CVD, HF, CVD death, and mortality increased with increasing BMI, with associations more apparent in men than in women. After exclusion of factors associated with reverse causality, there was no evidence of an obesity paradox.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c425d068b0f9ddace62d5a473e0f947Test
https://doi.org/10.1530/ey.16.10.16Test

المؤلفون: Weiqing Wang, Lingyun Tang, Zhugang Wang, Jie Hong, Guang Ning, Yingkai Sun, Rui Wang, Ruixin Liu, Jiqiu Wang, Wen Liu, Wen Li, Shaoqian Zhao

المصدر: Journal of Molecular Endocrinology. 62:79-90

مصطلحات موضوعية: Adult, Fibroblast Growth Factor 9, Male, 0301 basic medicine, medicine.medical_specialty, FGF21, Adolescent, Adipose Tissue, White, Adipocytes, White, Adipose tissue, White adipose tissue, Biology, Fibroblast growth factor, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Adipose Tissue, Brown, Internal medicine, Adipocyte, medicine, Animals, Humans, Obesity, RNA, Messenger, Molecular Biology, Gene knockdown, Cell Differentiation, Thermogenesis, Stromal vascular fraction, Hypoxia-Inducible Factor 1, alpha Subunit, Mice, Inbred C57BL, stomatognathic diseases, 030104 developmental biology, Gene Expression Regulation, chemistry, Female, 030217 neurology & neurosurgery, Signal Transduction

الوصف: Browning of white adipose tissue has been proven to be a potential target to fight against obesity and its metabolic commodities, making the exploration of molecules involved in browning process important. Among those browning agents reported recently, FGF21 play as a quite promising candidate for treating obesity for its obvious enhancement of thermogenic capacity in adipocyte and significant improvement of metabolic disorders in both mice and human. However, whether other members of fibroblast growth factor (FGF) family play roles in adipose thermogenesis and obese development is still an open question. Here, we examined the mRNA expression of all FGF family members in three adipose tissues of male C57BL/6 mice and found that FGF9 is highly expressed in adipose tissue and decreased under cold stress. Furthermore, FGF9 treatment inhibited thermogenic genes in the process of beige adipocytes differentiation from stromal vascular fraction (SVF) in a dose-dependent manner. Similar results were obtained with FGF9 overexpression. Consistently, knockdown of FGF9 in SVF cells by using lentiviral shRNA increased thermogenic genes in differentiated beige adipocytes. RNA sequencing analysis revealed a significant increment of hypoxia-inducible factor (HIF) pathway in the early stage of beige adipocytes differentiation under FGF9 treatment, which was validated by real-time PCR. FGF9 expression was increased in subcutaneous WAT of obese human and mice. This study shows that adipose-derived FGF9 play as an inhibitory role in the browning of white adipocytes. Activation of hypoxia signaling at early stage of adipose browning process may contribute to this anti-thermogenic effect of FGF9.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3885669eb3441f7a2c94123353756f5aTest
https://doi.org/10.1530/jme-18-0151Test

المؤلفون: Torben Hansen, Jinyi Zhang, Elizaveta L. Hansen, Signe S. Torekov, Sten Madsbad, Jens J. Holst, Mette Hollensted, Jens-Christian Holm, Henrik S. Thomsen, Eva W. Iepsen

المصدر: Yearbook of Paediatric Endocrinology.

مصطلحات موضوعية: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Physiology, media_common.quotation_subject, Appetite, 030209 endocrinology & metabolism, Glucagon-Like Peptide-1 Receptor, 03 medical and health sciences, 0302 clinical medicine, Weight loss, Internal medicine, Weight Loss, medicine, Humans, Hypoglycemic Agents, Obesity, Receptor, Molecular Biology, Glucagon-like peptide 1 receptor, media_common, business.industry, Liraglutide, Cell Biology, Middle Aged, medicine.disease, Melanocortin 4 receptor, 030104 developmental biology, Postprandial, Endocrinology, Mutation, Receptor, Melanocortin, Type 4, Female, medicine.symptom, business, medicine.drug

الوصف: Summary Pathogenic mutations in the appetite-regulating melanocortin-4 receptor (MC4R) represent the most common cause of monogenic obesity with limited treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) cause weight loss by reducing appetite. We assessed the effect of the GLP-1 RA liraglutide 3.0 mg for 16 weeks in 14 obese individuals with pathogenic MC4R mutations (BMI 37.5 ± 6.8) and 28 matched control participants without MC4R mutation (BMI 36.8 ± 4.8). Liraglutide decreased body weight by 6.8 kg ± 1.8 kg in individuals with pathogenic MC4R mutations and by 6.1 kg ± 1.2 kg in control participants. Total body fat, waist circumference, and fasting and postprandial glucose concentrations similarly decreased in both groups. Thus, liraglutide induced an equal, clinically significant weight loss of 6% in both groups, indicating that the appetite-reducing effect of liraglutide is preserved in MC4R causal obesity and that liraglutide acts independently of the MC4R pathway. Thus, liraglutide could be an effective treatment of the most common form of monogenic obesity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::34ed334ab8f55dd89ab7e32e31ba5c3dTest
https://doi.org/10.1530/ey.16.11.12Test

المؤلفون: Daniel Novák, Terezie Pelikanova, P Kaválková, Anna Cinkajzlová, Milos Mraz, Libor Vítek, Vaclav Burda, Zdeňka Lacinová, Marek Benes, Martin Haluzik, Jana Klouckova, Zuzana Vlasáková, Denisa Haluzikova, T. Petr, P Trachta

المصدر: Journal of Endocrinology. 231:11-22

مصطلحات موضوعية: Adult, Blood Glucose, Male, medicine.medical_specialty, Time Factors, Duodenum, Endocrinology, Diabetes and Metabolism, Bariatric Surgery, 030209 endocrinology & metabolism, Bile Acids and Salts, Duodenal-jejunal bypass liner, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Glucagon-Like Peptide 1, Weight loss, Internal medicine, White blood cell, Weight Loss, medicine, Humans, Obesity, Postoperative Period, Aged, Glycemic, business.industry, Type 2 Diabetes Mellitus, FGF19, Middle Aged, Postprandial Period, Lipids, Fibroblast Growth Factors, Jejunum, Treatment Outcome, medicine.anatomical_structure, Postprandial, Diabetes Mellitus, Type 2, Female, 030211 gastroenterology & hepatology, Blood sugar regulation, medicine.symptom, business

الوصف: Duodenal–jejunal bypass liner (DJBL) is an endoscopically implantable device designed to noninvasively mimic the effects of gastrointestinal bypass operations by excluding the duodenum and proximal jejunum from the contact with ingested food. The aim of our study was to assess the influence of DJBL on anthropometric parameters, glucose regulation, metabolic and hormonal profile in obese patients with type 2 diabetes mellitus (T2DM) and to characterize both the magnitude and the possible mechanisms of its effect. Thirty obese patients with poorly controlled T2DM underwent the implantation of DJBL and were assessed before and 1, 6 and 10months after the implantation, and 3months after the removal of DJBL. The implantation decreased body weight, and improved lipid levels and glucose regulation along with reduced glycemic variability. Serum concentrations of fibroblast growth factor 19 (FGF19) and bile acids markedly increased together with a tendency to restoration of postprandial peak of GLP1. White blood cell count slightly increased and red blood cell count decreased throughout the DJBL implantation period along with decreased ferritin, iron and vitamin B12 concentrations. Blood count returned to baseline values 3months after DJBL removal. Decreased body weight and improved glucose control persisted with only slight deterioration 3months after DJBL removal while the effect on lipids was lost. We conclude that the implantation of DJBL induced a sustained reduction in body weight and improvement in regulation of lipid and glucose. The increase in FGF19 and bile acids levels could be at least partially responsible for these effects.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6f75014dce1f5e2ecd972d6d9002e1baTest
https://doi.org/10.1530/joe-16-0206Test

المؤلفون: Anita Lavarda Scheinpflug, Kevin N. Keane, Mario J. Soares, Robson Cordeiro, Philip Newsholme, Vinicius Fernandes Cruzat

المصدر: Journal of Endocrinology. 224:261-271

مصطلحات موضوعية: Adult, Lipopolysaccharides, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Inflammation, Endocrinology, Insulin-Secreting Cells, Internal medicine, medicine, Humans, Obesity, Cells, Cultured, biology, Sirtuin 1, Macrophages, Insulin, Dipeptides, Middle Aged, Glutathione, Glutamine, Interleukin 10, Cytokine, biology.protein, Cytokines, Female, Tumor necrosis factor alpha, Inflammation Mediators, medicine.symptom, Oxidation-Reduction, Ex vivo

الوصف: Obesity-associated diabetes and concomitant inflammation may compromise pancreatic β-cell integrity and function. l-glutamine and l-alanine are potent insulin secretagogues, with antioxidant and cytoprotective properties. Herein, we studied whether the dipeptide l-alanyl-l-glutamine (Ala-Gln) could exert protective effects via sirtuin 1/HUR (SIRT1/HUR) signalling in β-cells, against detrimental responses following ex vivo stimulation with inflammatory mediators derived from macrophages (IMMs). The macrophages were derived from blood obtained from obese subjects. Macrophages were exposed (or not) to lipopolysaccharide (LPS) to generate a pro-inflammatory cytokine cocktail. The cytokine profile was determined following analysis by flow cytometry. Insulin-secreting BRIN–BD11 β-cells were exposed to IMMs and then cultured with or without Ala-Gln for 24 h. Chronic insulin secretion, the l-glutamine–glutathione (GSH) axis, and the level of insulin receptor β (IR-β), heat shock protein 70 (HSP70), SIRT1/HUR, CCAAT-enhancer-binding protein homologous protein (CHOP) and cytochrome c oxidase IV (COX IV) were evaluated. Concentrations of cytokines, including interleukin 1β (IL1β), IL6, IL10 and tumour necrosis factor alpha (TNFα) in the IMMs, were higher following exposure to LPS. Subsequently, when β-cells were exposed to IMMs, chronic insulin secretion, and IR-β and COX IV levels were decreased, but these effects were partially or fully attenuated by the addition of Ala-Gln. The glutamine–GSH axis and HSP70 levels, which were compromised by IMMs, were also restored by Ala-Gln, possibly due to protection of SIRT1/HUR levels, and a reduction of CHOP expression. Using an ex vivo inflammatory approach, we have demonstrated Ala-Gln-dependent β-cell protection mediated by coordinated effects on the glutamine–GSH axis, and the HSP pathway, maintenance of mitochondrial metabolism and stimulus–secretion coupling essential for insulin release.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a40e9c6f60679de42c217682ecf73eefTest
https://doi.org/10.1530/joe-14-0677Test

المؤلفون: Mark J. Bailey, Gregory E. Rice, Karen Oliva, Clyde Riley, Michael Permezel, Martha Lappas, Gillian Barker

المصدر: Journal of Molecular Endocrinology. 48:139-149

مصطلحات موضوعية: Adult, Proteomics, Proteome, Placenta, Protein subunit, Brain Acid Soluble Protein 1, Difference gel electrophoresis, Biology, Body Mass Index, Two-Dimensional Difference Gel Electrophoresis, Endocrinology, Western blot, Pregnancy, medicine, Humans, Obesity, Molecular Biology, medicine.diagnostic_test, Cesarean Section, Proteins, Maternal Nutritional Physiological Phenomena, Glucose Tolerance Test, Molecular biology, Ferritin light chain, medicine.anatomical_structure, Prenatal Exposure Delayed Effects, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Female

الوصف: Our aim was to study the protein expression profiles of placenta obtained from lean and obese pregnant women with normal glucose tolerance at the time of term Caesarean section. We used two-dimensional difference gel electrophoresis (2D-DIGE), utilising narrow-range immobilised pH gradient strips that encompassed the broad pH range of 4–5 and 5–6, followed by MALDI-TOF mass spectrometry of selected protein spots. Western blot and quantitative RT-PCR (qRT-PCR) analyses were performed to validate representative findings from the 2D-DIGE analysis. Eight proteins were altered (six down-regulated and two up-regulated on obese placentas). Annexin A5 (ANXA5), ATP synthase subunit beta, mitochondria (ATPB), brain acid soluble protein 1 (BASP1), ferritin light chain (FTL), heterogeneous nuclear ribonucleoprotein C (HNRPC) and vimentin (VIME) were all lower in obese patients. Alpha-1-antitrypsin (A1AT) and stress-70 protein, mitochondrial (GRP75) were higher in obese patients. Western blot analysis of ANXA5, ATPB, FTL, VIME, A1AT and GRP75 confirmed the findings from the 2D-DIGE analysis. For brain acid soluble protein 1 and HNRPC, qRT-PCR analysis also confirmed the findings from the 2D-DIGE analysis. Immunohistochemical analysis was also used to determine the localisation of the proteins in human placenta. In conclusion, proteomic analysis of placenta reveals differential expression of several proteins in patients with pre-existing obesity. These proteins are implicated in a variety of cellular functions such as regulation of growth, cytoskeletal structure, oxidative stress, inflammation, coagulation and apoptosis. These disturbances may have significant implications for fetal growth and development.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6f10be5d381ebbec564849d6c2108fc7Test
https://doi.org/10.1530/jme-11-0123Test

المؤلفون: Eric S. Kilpatrick, Rebecca V. Vince, Stephen L. Atkin, Alan S. Rigby, Anne Marie Coady, Hassan Kahal, Tamas Ungvari, Khalid M. Naseem, Ahmed Aburima, Ramzi A. Ajjan

المصدر: BMC Endocrine Disorders

مصطلحات موضوعية: Adult, Blood Platelets, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Urinary system, Carotid Intima-Media Thickness, Young Adult, chemistry.chemical_compound, Insulin resistance, Glucagon-Like Peptide 1, Risk Factors, Weight loss, Diabetes mellitus, Internal medicine, PCOS, Humans, Hypoglycemic Agents, Medicine, Obesity, Young adult, Reactive hyperemia, Triglyceride, business.industry, Liraglutide, Fibrinolysis, General Medicine, Middle Aged, medicine.disease, Polycystic ovary, Confidence interval, Endocrinology, chemistry, Cardiovascular Diseases, cIMT, Female, Platelet function, Insulin Resistance, medicine.symptom, business, Polycystic Ovary Syndrome, Research Article, medicine.drug

الوصف: Background Polycystic ovary syndrome (PCOS) is associated with obesity and increased cardiovascular (CV) risk markers. In this study our aim was to assess the effects of six months treatment with liraglutide 1.8 mg od on obesity, and CV risk markers, particularly platelet function, in young obese women with PCOS compared to controls of similar age and weight. Methods Carotid intima-media wall thickness (cIMT) was measured by B-mode ultrasonography, platelet function by flow cytometry, clot structure/lysis by turbidimetric assays and endothelial function by ELISA and post-ischaemic reactive hyperemia (RHI). Data presented as mean change (6-month – baseline) ± standard deviation. Results Nineteen obese women with PCOS and 17 controls, of similar age and weight, were recruited; baseline atherothrombotic risk markers did not differ between the two groups. Twenty five (69.4%) participants completed the study (13 PCOS, 12 controls). At six months, weight was significantly reduced by 3.0 ± 4.2 and 3.8 ± 3.4 kg in the PCOS and control groups, respectively; with no significant difference between the two groups, P = 0.56. Similarly, HOMA-IR, triglyceride, hsCRP, urinary isoprostanes, serum endothelial adhesion markers (sP-selectin, sICAM and sVCAM), and clot lysis area were equally significantly reduced in both groups compared to baseline. Basal platelet P-selectin expression was significantly reduced at six months in controls −0.17 ± 0.26 but not PCOS −0.12 ± 0.28; between groups difference, 95% confidence interval = −0.14 – 0.26, P = 0.41. No significant changes were noted in cIMT or RHI. Conclusions Six months treatment with liraglutide (1.8 mg od) equally affected young obese women with PCOS and controls. In both groups, liraglutide treatment was associated with 3–4% weight loss and significant reduction in atherothrombosis markers including inflammation, endothelial function and clotting. Our data support the use of liraglutide as weight loss medication in simple obesity and suggest a potential beneficial effect on platelet function and atherothrombotic risk at 6 months of treatment. Trial registration Clinical trial reg. no. ISRCTN48560305. Date of registration 22/05/2012.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ba2e4a48671afff7e168485184e24957Test
https://doi.org/10.1530/endoabs.34.p229Test

المؤلفون: Susan Bonner-Weir

المصدر: Journal of Molecular Endocrinology. 24:297-302

مصطلحات موضوعية: Adult, medicine.medical_specialty, endocrine system diseases, Apoptosis, Disease, Carbohydrate metabolism, Islets of Langerhans, Endocrinology, Insulin resistance, Diabetes mellitus, Internal medicine, Acromegaly, medicine, Animals, Humans, Molecular Biology, geography, geography.geographical_feature_category, business.industry, nutritional and metabolic diseases, medicine.disease, Islet, Obesity, Diabetes Mellitus, Type 1, Glucose, Diabetes Mellitus, Type 2, Insulin Resistance, business, Cell Division, Cell mass

الوصف: Diabetes mellitus, whether type 1 (insulindependent diabetes mellitus; IDDM) or type 2 (noninsulin-dependent diabetes mellitus; NIDDM) results from an inadequate mass of functional pancreatic -cells. In the first case, the -cell mass is reduced by the autoimmune destruction of the -cells, while, in the latter, there is incomplete compensation to meet the demand often imposed by insulin resistance. This latter point is not always appreciated. However, only 20% of those people with severe insulin resistance due to obesity, Cushing’s disease, or acromegaly become diabetic, with the other 80% being able to compensate to

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c2c3b33ad73e00761e4b5ba8170f866bTest
https://doi.org/10.1677/jme.0.0240297Test