AIMTo identify genes that are differentially expressed in omental fat of normal weight subjects, obese subjects and obese type 2 diabetic patients.

METHODSUsing a home-made high-density cDNA microarray, we compared gene expression profile of omental fat from normal weigh subjects, obese subjects and obese type 2 diabetic patients, to identify adipose-specific genes associated with obesity and diabetes.

RESULTS119 and 257 genes were up-regulated in obese patients and obese diabetic patients respectively, while 46 and 58 genes were down-regulated in obese patients and obese diabetic patients respectively. 77 genes, including metabolism related genes (PDK4), and caveolin 2, metallo thionein 1B, were up-regulated in both obese and obese diabetic patients, while 8 genes, including key enzymes in lipid synthesis, such as HMG-CoA synthase, fatty acid synthase and stearoyl-CoA desaturase, were down-regulated in both groups. Another interesting finding was that tyrosine-3-monooxygenase/ tryptophan 5-monooxygenase activation protein theta (YWHAZ), a negative regulator for insulin signal transduction, was up-regulated only in obese diabetic patient, but not in normal-glycemic obese subjects.

CONCLUSIONOur study demonstrated that decrease of lipogenesis along with increase of fatty acids oxidation of adipose tissue could be a common cause of insulin resistance in obesity and type 2 diabetes, while functional changes of other genes, such as immune regulation genes,might also be involved in the pathogenesis of obesity and type 2 diabetes. Block of insulin signal transduction might trigger the transition from obesity to diabetes. Further exploration of these genes will greatly help us in the understanding of the pathogenesis of obesity and type 2 diabetes.

Abdominal Fat ; metabolism ; Adipose Tissue ; metabolism ; Adult ; Diabetes Mellitus, Type 2 ; genetics ; metabolism ; Female ; Gene Expression Profiling ; Humans ; Insulin ; metabolism ; Insulin Resistance ; Male ; Middle Aged ; Obesity ; genetics ; metabolism ; Oligonucleotide Array Sequence Analysis