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

Severine G. Dubois, Leonie K. Heilbronn, Steven R. Smith, Jeanine B. Albu, David E. Kelley, Eric Ravussin

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

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) a, 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 a, sterol regulatory element-binding protein le (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 in dividuals 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 uμm; 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/EBP/β 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.

Original languageEnglish
Pages (from-to)1543-1552
Number of pages10
JournalObesity
Volume14
Issue number9
DOIs
StatePublished - Sep 2006
Externally publishedYes

Keywords

  • Adipogenesis
  • Fat cell size
  • Gene expression
  • Insulin resistance
  • Type 2 diabetes

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