Worsening of Obesity and Metabolic Status Yields Similar Molecular Adaptations in Human Subcutaneous and Visceral Adipose Tissue: Decreased Metabolism and Increased Immune Response

• Published in: The journal of clinical endocrinology and metabolism 2011-01, Vol.96 (1), p.E73-E82
• Main Authors: Klimčáková, Eva, Roussel, Balbine, Márquez-Quiñones, Adriana, Kováčová, Zuzana, Kováčiková, Michaela, Combes, Marion, Šiklová-Vítková, Michaela, Hejnová, Jindra, Šrámková, Petra, Bouloumié, Anne, Viguerie, Nathalie, Štich, Vladimir, Langin, Dominique
• Format: Article
• Language: English
• Subjects: Adaptations; Adipose tissue; Adult; Aged; Amino acids; Apoptosis; Blood; Body fat; Body weight; Carbohydrates; Computed tomography; DNA microarrays; Down-Regulation; Energy metabolism; Fats; Fatty acids; Female; Gene Expression; Gene Expression - immunology; Glucose Clamp Technique; Hormones; Hospitals; Humans; Immune response; Insulin; Insulin Resistance; Intra-Abdominal Fat; Intra-Abdominal Fat - immunology; Intra-Abdominal Fat - metabolism; Lipids; Measurement; Metabolic disorders; Metabolic pathways; Metabolic Syndrome - genetics; Metabolic Syndrome - immunology; Metabolic Syndrome - metabolism; Metabolic Syndrome X; Metabolism; Middle Aged; Mitochondria; Obesity; Obesity - genetics; Obesity - immunology; Obesity - metabolism; Pathogenicity; Subcutaneous Fat; Subcutaneous Fat - immunology; Subcutaneous Fat - metabolism; Toll-like receptors; Tumor necrosis factor; Women
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2010-1575

Context: It is not known whether biological differences reported between sc adipose tissue (SAT) and visceral adipose tissue (VAT) depots underlie the pathogenicity of visceral fat. Objective: We compared SAT and VAT gene expression according to obesity, visceral fat accumulation, insulin resistance, and presence of the metabolic syndrome. Design: Subjects were assigned into four groups (lean, overweight, obese, and obese with metabolic syndrome). Setting: Subjects were recruited at a university hospital. Patients: Thirty-two women were included. Main Outcome Measures: Anthropometric measurements, euglycemic-hyperinsulinemic clamps, blood analyses, and computed tomography scans were performed, and paired samples of SAT and VAT were obtained for DNA microarray-based gene expression profiling. Results: Considering the two fat depots together, 1125 genes were more and 1025 genes were less expressed in lean compared with metabolic syndrome subjects. Functional annotation clustering showed, from lean to metabolic syndrome subjects, progressive down-regulation of metabolic pathways including branched-chain amino acid, fatty acid, carbohydrate, and mitochondrial energy metabolism and up-regulation of immune response genes involved in toll-like receptor, TNF, nuclear factor-κB, and apoptosis pathways. Metabolism and immune response genes showed an opposite correlation with fat mass, fat distribution, or insulin resistance indices. These associations were similar in SAT and VAT, although about 1000 genes showed differential expression between SAT and VAT. Conclusions: The increase in adiposity and the worsening of metabolic status are associated with a coordinated down-regulation of metabolism-related and up-regulation of immune response-related gene expression. Molecular adaptations in SAT prove as discriminating as those in VAT. In subcutaneous and visceral adipose tissues, obesity and metabolic syndrome are associated with downregulation of metabolism-related gene expression and upregulation of immune response-related gene expression.