Decreased Expression of Adipogenic Genes in Obese Subjects with Type 2 Diabetes

• Published in: Obesity (Silver Spring, Md.) Vol. 14; no. 9; pp. 1543 - 1552
• Main Authors: Dubois, Severine G, Heilbronn, Leonie K, Smith, Steven R, Albu, Jeanine B, Kelley, David E, Ravussin, Eric
• Format: Journal Article
• Language: English
• Published: Oxford, UK The North American Association for the Study of Obesity 01.09.2006; Blackwell Publishing Ltd
• Subjects: Adipocytes; adipogenesis; Adipose Tissue - cytology; Adipose Tissue - metabolism; Adult; Aged; Biomedical research; Body fat; Case-Control Studies; CCAAT-Enhancer-Binding Proteins - metabolism; Cell Differentiation - genetics; Cell Division - genetics; Cross-Sectional Studies; Dehydrogenases; Diabetes; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; diet-related diseases; fat cell size; fat free mass; Female; Gene expression; gene overexpression; Glucose; Glucose Clamp Technique; Humans; Insulin Resistance; Insulin-like growth factors; Intercellular Signaling Peptides and Proteins - metabolism; lipogenesis; Male; Middle Aged; noninsulin-dependent diabetes mellitus; Obesity; Obesity - genetics; Obesity - metabolism; obesity-related diseases; overweight; PPAR gamma - metabolism; Proteins; Research methodology; Sterol Regulatory Element Binding Protein 1 - metabolism; Sterols; Tumor necrosis factor-TNF; type 2 diabetes; Weight control; New York; Pittsburgh Pennsylvania; Baton Rouge Louisiana; United States > US
• ISSN: 1071-7323; 1930-7381; 1930-739X
• DOI: 10.1038/oby.2006.178

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) α, C/EBPδ, GATA domain-binding protein 3 (GATA3), C/EBPβ, peroxisome proliferator-activated receptor (PPAR) γ2, signal transducer and activator of transcription 5A (STAT5A), Wnt-10b, tumor necrosis factor α, sterol regulatory element-binding protein 1c (SREBP1c), 11 beta-hydroxysteroid dehydrogenase, PPARG angiopoietin-related protein (PGAR), insulin-like growth factor 1, PPARγ coactivator 1α, PPARγ coactivator 1β, and PPARδ] 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 μm; p = 0.04) as compared with obese control subjects. Three genes (SREBP1c, p < 0.01; STAT5A, p = 0.02; and PPARγ2, p = 0.02) had significantly lower expression in obese type 2 diabetics, whereas C/EBPβ 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.