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


METHODS
We examined the expression of candidate genes involved in adipocyte proliferation and/or differentiation [CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBPdelta, GATA domain-binding protein 3 (GATA3), C/EBPbeta, peroxisome proliferator-activated receptor (PPAR) gamma2, signal transducer and activator of transcription 5A (STAT5A), Wnt-10b, tumor necrosis factor alpha, sterol regulatory element-binding protein 1c (SREBP1c), 11 beta-hydroxysteroid dehydrogenase, PPARG angiopoietin-related protein (PGAR), insulin-like growth factor 1, PPARgamma coactivator 1alpha, PPARgamma coactivator 1beta, and PPARdelta] 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 microm; p = 0.04) as compared with obese control subjects. Three genes (SREBP1c, p < 0.01; STAT5A, p = 0.02; and PPARgamma2, p = 0.02) had significantly lower expression in obese type 2 diabetics, whereas C/EBPbeta only tended to be lower (p = 0.07).


CONCLUSIONS
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.
Dubois
Severine G
SG
Health and Performance Enhancement Division, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
Heilbronn
Leonie K
LK
Smith
Steven R
SR
Albu
Jeanine B
JB
Kelley
David E
DE
Ravussin
Eric
E
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000328:Adult; D000368:Aged; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000235:genetics*; D002455:Cell Division / Q000235:genetics*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047495:PPAR gamma; D051780:Sterol Regulatory Element Binding Protein 1