Insulin-mimetic compound hexaquis (benzylammonium) decavanadate is antilipolytic in human fat cells

This study investigates in murine and human adipocytes the antilipolytic properties of a conjugate of benzylamine and decavanadate (B6V10), already reported to lower hyperglycaemia in diabetic rodents. Data indicated that the conjugate dose-dependently inhibited submaximal activation of lipolysis in all the species studied. Such antilipolytic action deals with the in vivo FFA-lowering properties already described for B6V10 in diabetic rats. B6V10 also activated lipogenesis and glucose transport in fat cells. B6V10 should therefore be useful in preventing the lipotoxicity constituted by the unrestrained lipolytic activity of insulin-resistant adipocytes in obese individuals presenting type 2 diabetes, a state named diabesity

Macrophages and Adipocytes in Human Obesity: Adipose Tissue Gene Expression and Insulin Sensitivity During Calorie Restriction and Weight Stabilization

International audienceOBJECTIVE: We investigated the regulation of adipose tissue gene expression during different phases of a dietary weight loss program and its relation with insulin sensitivity. RESEARCH DESIGN AND METHODS: Twenty-two obese women followed a dietary intervention program composed of an energy restriction phase with a 4-week very-low-calorie diet and a weight stabilization period composed of a 2-month low-calorie diet followed by 3-4 months of a weight maintenance diet. At each time point, a euglycemic-hyperinsulinemic clamp and subcutaneous adipose tissue biopsies were performed. Adipose tissue gene expression profiling was performed using a DNA microarray in a subgroup of eight women. RT-quantitative PCR was used for determination of mRNA levels of 31 adipose tissue macrophage markers (n = 22). RESULTS: Body weight, fat mass, and C-reactive protein level decreased and glucose disposal rate increased during the dietary intervention program. Transcriptome profiling revealed two main patterns of variations. The first involved 464 mostly adipocyte genes involved in metabolism that were downregulated during energy restriction, upregulated during weight stabilization, and unchanged during the dietary intervention. The second comprised 511 mainly macrophage genes involved in inflammatory pathways that were not changed or upregulated during energy restriction and downregulated during weight stabilization and dietary intervention. Accordingly, macrophage markers were upregulated during energy restriction and downregulated during weight stabilization and dietary intervention. The increase in glucose disposal rates in each dietary phase was associated with variation in expression of sets of 80-110 genes that differed among energy restriction, weight stabilization, and dietary intervention. CONCLUSIONS: Adipose tissue macrophages and adipocytes show distinct patterns of gene regulation and association with insulin sensitivity during the various phases of a dietary weight loss program

TGFbeta Family Members Are Key Mediators in the Induction of Myofibroblast Phenotype of Human Adipose Tissue Progenitor Cells by Macrophages

International audienceOBJECTIVE: The present study was undertaken to characterize the remodeling phenotype of human adipose tissue (AT) macrophages (ATM) and to analyze their paracrine effects on AT progenitor cells. RESEARCH DESIGN AND METHODS: The phenotype of ATM, immunoselected from subcutaneous (Sc) AT originating from subjects with wide range of body mass index and from paired biopsies of Sc and omental (Om) AT from obese subjects, was studied by gene expression analysis in the native and activated states. The paracrine effects of ScATM on the phenotype of human ScAT progenitor cells (CD34(+)CD31(-)) were investigated. RESULTS: Two main ATM phenotypes were distinguished based on gene expression profiles. For ScAT-derived ATM, obesity and adipocyte-derived factors favored a pro-fibrotic/remodeling phenotype whereas the OmAT location and hypoxic culture conditions favored a pro-angiogenic phenotype. Treatment of native human ScAT progenitor cells with ScATM-conditioned media induced the appearance of myofibroblast-like cells as shown by expression of both α-SMA and the transcription factor SNAIL, an effect mimicked by TGFβ1 and activinA. Immunohistochemical analyses showed the presence of double positive α-SMA and CD34 cells in the stroma of human ScAT. Moreover, the mRNA levels of SNAIL and SLUG in ScAT progenitor cells were higher in obese compared with lean subjects. CONCLUSIONS: Human ATM exhibit distinct pro-angiogenic and matrix remodeling/fibrotic phenotypes according to the adiposity and the location of AT, that may be related to AT microenvironment including hypoxia and adipokines. Moreover, human ScAT progenitor cells have been identified as target cells for ScATM-derived TGFβ and as a potential source of fibrosis through their induction of myofibroblast-like cells

Human visceral-fat-specific glucocorticoid tuning of adipogenesis.

International audienceCentral obesity and long-term glucocorticoid exposure are both characterized by visceral fat enlargement and increased risk for metabolic diseases. In this issue of Cell Metabolism, Lindroos et al. identify LIM domain only 3 as a molecular partner for glucocorticoids required for adipocyte differentiation specifically in human visceral fat

Etude des synthases du monoxyde d'azote dans le tissu adipeux blanc

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Les métalloprotéases matricielles 2 et 9 et la différenciation des cellules progénitrices du tissu adipeux humain

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Les lymphocytes du tissu adipeux humain (caractérisation et rôles)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

The Sexual Dimorphism of Human Adipose Depots

The amount and the distribution of body fat exhibit trajectories that are sex- and human species-specific and both are determinants for health. The enhanced accumulation of fat in the truncal part of the body as a risk factor for cardiovascular and metabolic diseases is well supported by epidemiological studies. In addition, a possible independent protective role of the gluteofemoral fat compartment and of the brown adipose tissue is emerging. The present narrative review summarizes the current knowledge on sexual dimorphism in fat depot amount and repartition and consequences on cardiometabolic and reproductive health. The drivers of the sex differences and fat depot repartition, considered to be the results of complex interactions between sex determination pathways determined by the sex chromosome composition, genetic variability, sex hormones and the environment, are discussed. Finally, the inter- and intra-depot heterogeneity in adipocytes and progenitors, emphasized recently by unbiased large-scale approaches, is highlighted