Project description:ObjectiveEndurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown.MethodsIn the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine-alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls.ResultsHIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content.ConclusionsThese data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC.
Project description:During skin aging, the volume of subcutaneous adipose tissue (sWAT) and the adipogenesis potential of adipose-derived stem cells (ASCs) decrease. It is known that the shortening of cilia length by pro-inflammatory cytokines is related to the decreased adipogenic differentiation of ASCs via increase in Wnt5a/β-catenin. High-intensity focused ultrasound (HIFU) is known to upregulate heat shock proteins (HSP), which decrease levels of pro-inflammatory cytokines. In this study, we evaluated whether HIFU modulates the cilia of ASCs by upregulating HSP70 and decreasing inflammatory cytokines. HIFU was applied at 0.2 J to rat skin, which was harvested at 1, 3, 7, and 28 days. All results for HIFU-applied animals were compared with control animals that were not treated. HIFU increased expression of HSP70 and decreased expression of NF-κB, IL-6, and TNF-α in sWAT. HIFU decreased the expression of cilia disassembly-related factors (AurA and HDAC9) in ASCs. Furthermore, HIFU increased the expression of cilia assembly-related factors (KIF3A and IFT88), decreased that of WNT5A/β-catenin, and increased that of the adipogenesis markers PPARγ and CEBPα in sWAT. HIFU increased the number of adipocytes in the sWAT and the thickness of sWAT. In conclusion, HIFU could selectively increase sWAT levels by modulating the cilia of ASCs and be used for skin rejuvenation.
Project description:The menopausal transition is accompanied by changes in adipose tissue storage, leading to an android body composition associated with increased risk of type 2 diabetes and cardiovascular disease in post-menopausal women. Estrogens probably affect local adipose tissue depots differently. We investigated how menopausal status and exercise training influence adipose tissue mass, adipose tissue insulin sensitivity and adipose tissue proteins associated with lipogenesis/lipolysis and mitochondrial function. Healthy, normal-weight pre- (n = 21) and post-menopausal (n = 20) women participated in high-intensity exercise training three times per week for 12 weeks. Adipose tissue distribution was determined by dual-energy x-ray absorptiometry and magnetic resonance imaging. Adipose tissue glucose uptake was assessed by positron emission tomography/computed tomography (PET/CT) by the glucose analog [18F]fluorodeoxyglucose ([18F]FDG) during continuous insulin infusion (40 mU·m-2·min-1). Protein content associated with insulin signaling, lipogenesis/lipolysis, and mitochondrial function were determined by western blotting in abdominal and femoral white adipose tissue biopsies. The mean age difference between the pre- and the post-menopausal women was 4.5 years. Exercise training reduced subcutaneous (~4%) and visceral (~6%) adipose tissue masses similarly in pre- and post-menopausal women. Insulin-stimulated glucose uptake, assessed by [18F]FDG-uptake during PET/CT, was similar in pre- and post-menopausal women in abdominal, gluteal, and femoral adipose tissue depots, despite skeletal muscle insulin resistance in post- compared to pre-menopausal women in the same cohort. Insulin-stimulated glucose uptake in adipose tissue depots was not changed after 3 months of high-intensity exercise training, but insulin sensitivity was higher in visceral compared to subcutaneous adipose tissue depots (~139%). Post-menopausal women exhibited increased hexokinase and adipose triglyceride lipase content in subcutaneous abdominal adipose tissue. Physical activity in the early post-menopausal years reduces abdominal obesity, but insulin sensitivity of adipose tissue seems unaffected by both menopausal status and physical activity.
Project description:We collected adipose tissue specimens during elective surgery (inguinal hernia, cryptorchism). Samples were proceesed for extraction of total RNA, using phenol:chlorophorm extraction. Next generation RNA sequencing were performed. Published article: https://www.mdpi.com/1422-0067/24/23/16706
Project description:Interactions between stromal cell-derived factor-1M-NM-1 (SDF-1M-NM-1) and its cognate receptor CXCR4 are crucial for the recruitment of mesenchymal stem cells (MSCs) from bone marrow (BM) reservoirs to damaged tissues for repair during alarm situations. MicroRNAs are differentially expressed in stem cell niches, suggesting a specialized role in stem cell regulation. Here, we gain insight into the molecular mechanisms involved in regulating SDF-1M-NM-1. Individualized outcome prediction classifiers were successfully constructed through expression profiling of microRNAs (in all organisms as annotated in Sanger miRBase Release 11.0 (http://microrna.sanger.ac.uk))in one burned murine skin tissue compared to normal skin tissue,which had 57 upregulated microRNAs and 28 down-regulated microRNAs. In the study presented here, a consecutively operated, well-defined cohort of 2 cases, was used to acquire expression profiles of microRNAs (in all organisms as annotated in Sanger miRBase Release 11.0 (http://microrna.sanger.ac.uk)), leading to the successful construction of supervised. The most recent version of the array (v.11.0 - hsa, mmu & rno array) contains more than 1700 capture probes, covering all microRNAs annotated in miRBase 11.0, as well as all viral microRNAs, related to these species.
Project description:This study compares the effect of two types of exercise training, i.e., moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT) on the browning of subcutaneous white adipose tissue (scWAT) in obese male rats. Effects on fat composition, metabolites, and molecular markers of differentiation and energy expenditure were examined. Forty male Wistar rats were assigned to lean (n = 8) or obese (n = 32) groups and fed either a standard chow or high-fat obesogenic diet for 10 weeks. Eight lean and obese rats were then blood and tissue sampled, and the remaining obese animals were randomly allocated into sedentary, MICT, or HIIT (running on a treadmill 5 days/week) groups that were maintained for 12 weeks. Obesity increased plasma glucose and insulin and decreased irisin and FGF-21. In scWAT, this was accompanied with raised protein abundance of markers of adipocyte differentiation, i.e., C/EBP-?, C/EBP-?, and PPAR-?, whereas brown fat-related genes, i.e., PRDM-16, AMPK/SIRT1/PGC-1?, were reduced as was UCP1 and markers of fatty acid transport, i.e., CD36 and CPT1. Exercise training increased protein expression of brown fat-related markers, i.e., PRDM-16, AMPK/SIRT1/PGC-1?, and UCP1, together with gene expression of fatty acid transport, i.e., CD36 and CPT1, but decreased markers of adipocyte differentiation, i.e., C/EBP-?, C/EBP-?, and plasma glucose. The majority of these adaptations were greater with HIIT compared to MICT. Our findings indicate that prolonged exercise training promotes the browning of white adipocytes, possibly through suppression of adipogenesis together with white to beige trans-differentiation and is dependent on the intensity of exercise.
Project description:White adipose tissue expands through both adipocyte hypertrophy and hyperplasia and it is hypothesized that fibrosis or excess accumulation of extracellular matrix within adipose tissue may limit tissue expansion contributing to metabolic dysfunction. The pathways that control adipose tissue remodeling are only partially understood, however it is likely that adipose tissue stromal and perivascular progenitors participate in fibrotic remodeling and also serve as adipocyte progenitors. The goal of this study was to investigate the role of the secreted extracellular matrix protein aortic carboxypeptidase-like protein (ACLP) on adipose progenitor differentiation in the context of adipose tissue fibrosis. Treatment of 10T1/2 mouse cells with recombinant ACLP suppressed adipogenesis and enhanced myofibroblast differentiation, which was dependent on transforming growth factor-β receptor kinase activity. Mice fed a chronic high fat diet exhibited white adipose tissue fibrosis with elevated ACLP expression and cellular fractionation of these depots revealed that ACLP was co-expressed with collagens primarily in the inflammatory cell depleted stromal-vascular fraction (SVF). SVF cells isolated from mice fed a high fat diet secreted increased amounts of ACLP compared to low fat diet control SVF. These cells also exhibited reduced adipogenic differentiation capacity in vitro. Importantly, differentiation studies in primary human adipose stromal cells revealed that mature adipocytes do not express ACLP and exogenous ACLP administration blunted their differentiation potential while upregulating myofibroblastic markers. Collectively, these studies identify ACLP as a stromal derived mediator of adipose progenitor differentiation that may limit adipocyte expansion during white adipose tissue fibrosis.
Project description:OBJECTIVE:This study aimed to characterize the differences in protein oxidation biomarkers in adipose tissue (AT) as an indicator of AT metabolism and bariatric surgery weight-loss success. METHODS:A human model, in which sixty-five individuals with obesity underwent bariatric surgery, and a diet-induced obesity animal model, in which animals were treated for 2 months with normocaloric diets, were analyzed to determine the associations between AT protein oxidation and body weight loss. Protein oxidative biomarkers were determined by gas chromatography/mass spectrometry in AT from human volunteers before the surgery, as well as 2 months after a diet treatment in the animal model. RESULTS:The levels of carboxyethyl-lysine (CEL) and 2-succinocystein (2SC) in both visceral and subcutaneous AT before the surgery directly correlated with greater weight loss in both human and animal models. 2SC levels in subcutaneous AT greater than 4.7 × 106 μmol/mol lysine (95% CI: 3.4 × 106 to 6.0 × 106 ) may predict greater weight loss after bariatric surgery (receiver operating characteristic curve area = 0.8222; P = 0.0047). Additionally, it was observed that individuals with diabetes presented lower levels of CEL and 2SC in subcutaneous AT (P = 0.0266 and P = 0.0316, respectively) compared with individuals without diabetes. CONCLUSIONS:CEL and 2SC in AT are useful biomarkers of AT metabolism and predict the individual's ability to reduce body weight after bariatric surgery.