DEPOT-RELATED GENE-EXPRESSION IN HUMAN SUBCUTANEOUS AND OMENTAL ADIPOCYTES

Human omental adipocytes display a range of biochemical properties tha t distinguish them from adipocytes of subcutaneous origin. However inf ormation about site-related gene expression in human fat cells is limi ted. We have previously demonstrated that leptin mRNA is markedly over expressed in abdominal subcutaneous (SC) compared with omental (Om) ad ipocytes. To further investigate depot-specific differences in adipocy te gene expression, we have measured, in paired samples of isolated hu man adipocytes obtained from SC and Om fat depots, the expression of m RNAs encoding a number of proteins involved in the control of adipocyt e metabolism. In contrast to the marked site-related expression of lep tin, genes encoding lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), tumor necrosis factor-alpha (TNF-alpha), and adipsin were not consist ently differentially expressed. Of note, a highly significant inverse correlation between adipocyte PPAR-gamma expression and BMI (r = -0.7, P = 0.0005) was found. In parallel experiments, differential display was used in an attempt to identify novel and/or unexpected adipocyte g enes that were expressed in a site-related manner. No transcript that was unique to one or another depot was found, but cellular inhibitor o f apoptosis protein-2 (cIAP2) mRNA, which has not previously been repo rted in adipocytes, was expressed at higher levels in Om than SC adipo cytes (Om > SC in all eight subjects; mean Om:SC ratio 1.9 +/- 0.2, P < 0.01). Because cIAP2 may be involved in the regulation of TNF-alpha signaling, this raises the possibility that depot-specific differences may exist in the regulation of adipocyte apoptosis. Thus, of the mRNA s examined to date, only leptin and cIAP2 show consistent site-related expression, suggesting that these molecules may have important roles in determining functional properties particular to individual adipose depots. Given the importance of PPAR-gamma in adipocyte development an d insulin sensitivity the inverse correlation between adipocyte PPAR-g amma mRNA levels and adiposity may represent a local regulatory mechan ism restraining fat accumulation and/or may be related to the reductio n of insulin sensitivity that occurs with increasing fat mass.