The expression of adipogenic genes is decreased in obesity and diabetes mellitus

Obesity is strongly correlated with type 2 diabetes mellitus, a common diso rder of glucose and lipid metabolism. Although adipocytes are critical in o besity, their role in diabetes has only recently been appreciated. We condu cted studies by using DNA microarrays to identify differences in gene expre ssion in adipose tissue from lean, obese, and obese-diabetic mice. The expr ession level of over 11,000 transcripts was analyzed, and 214 transcripts s howed significant differences between lean and obese mice. Surprisingly, th e expression of genes normally associated with adipocyte differentiation we re down-regulated in obesity. Not all obese individuals will become diabeti c; many remain normoglycemic despite profound obesity. Understanding the tr ansition to obesity with concomitant diabetes will provide important clues to the pathogenesis of type 2 diabetes. Therefore, we examined the levels o f gene expression in adipose tissue from five groups of obese mice with var ying degrees of hyperglycemia. and we identified 88 genes whose expression strongly correlated with diabetes severity. This group included many genes that are known to be involved in signal transduction and energy metabolism as well as genes not previously examined in the context of diabetes. Our da ta show that a decrease in expression of genes normally involved in adipoge nesis is associated with obesity, and we further identify genes important f or subsequent development of type 2 diabetes mellitus.