Decreased expression of adipogenic genes in obese subjects with type 2 diabetes

Abstract

OBJECTIVE: Our objective was to delineate the potential role of adipogenesis in insulin resistance and type 2 diabetes. Obesity is characterized by an increase in adipose tissue mass resulting from enlargement of existing fat cells (hypertrophy) and/or from increased number of adipocytes (hyperplasia). The inability of the adipose tissue to recruit new fat cells may cause ectopic fat deposition and insulin resistance. RESEARCH METHODS AND PROCEDURES: We examined the expression of candidate genes involved in adipocyte proliferation and/or differentiation [ CCAAT/enhancer-binding protein (C/EBP) , C/EBP , GATA domain-binding protein 3 (GATA3), C/EBP , peroxisome proliferator-activated receptor (PPAR) 2, signal transducer and activator of transcription 5A (STAT5A), Wnt-10b, tumor necrosis factor , sterol regulatory element-binding protein 1c (SREBP1c), 11 beta-hydroxysteroid dehydrogenase, PPARG angiopoietin-related protein (PGAR), insulin-like growth factor 1, PPAR coactivator 1 , PPAR coactivator 1 , and PPAR ] in subcutaneous adipose tissue from 42 obese individuals with type 2 diabetes and 25 non-diabetic subjects matched for age and obesity. RESULTS: Insulin sensitivity was measured by a 3-hour 80 mU/m2 per minute hyperinsulinemic glucose clamp (100 mg/dL). As expected, subjects with type 2 diabetes had lower glucose disposal (4.9 1.9 vs. 7.5 2.8 mg/min per kilogram fat-free mass; p < 0.001) and larger fat cells (0.90 0.26 vs. 0.78 0.17 m; p = 0.04) as compared with obese control subjects. Three genes (SREBP1c, p < 0.01; STAT5A, p = 0.02; and PPAR 2, p = 0.02) had significantly lower expression in obese type 2 diabetics, whereas C/EBP only tended to be lower (p = 0.07). DISCUSSION: This cross-sectional study supports the hypothesis that impaired expression of adipogenic genes may result in impaired adipogenesis, potentially leading to larger fat cells in subcutaneous adipose tissue and insulin resistance.