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

Obesity is strongly correlated with type 2 diabetes mellitus, a common disorder of glucose and lipid metabolism. Although adipocytes are critical in obesity, their role in diabetes has only recently been appreciated. We conducted studies by using DNA microarrays to identify differences in gene expression in adipose tissue from lean, obese, and obese-diabetic mice. The expression level of over 11,000 transcripts was analyzed, and 214 transcripts showed significant differences between lean and obese mice. Surprisingly, the expression of genes normally associated with adipocyte differentiation were down-regulated in obesity. Not all obese individuals will become diabetic; many remain normoglycemic despite profound obesity. Understanding the transition to obesity with concomitant diabetes will provide important clues to the pathogenesis of type 2 diabetes. Therefore, we examined the levels of gene expression in adipose tissue from five groups of obese mice with varying 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 data show that a decrease in expression of genes normally involved in adipogenesis is associated with obesity, and we further identify genes important for subsequent development of type 2 diabetes mellitus.

肥胖与2型糖尿病（type 2 diabetes mellitus）密切相关，后者是一种常见的糖脂代谢紊乱性疾病。尽管脂肪细胞在肥胖发生过程中发挥关键作用，但直至近年学界才逐渐认识到其在糖尿病发病中的功能。本研究利用DNA微阵列（DNA microarrays）技术，对瘦鼠、肥胖鼠及肥胖糖尿病小鼠的脂肪组织展开基因表达差异分析。本研究共分析了超过11000个转录本（transcripts）的表达水平，其中214个转录本在瘦鼠与肥胖鼠的脂肪组织中呈现显著表达差异。令人意外的是，通常与脂肪细胞分化相关的基因在肥胖状态下呈现表达下调。并非所有肥胖个体都会罹患糖尿病，部分个体即便存在重度肥胖，仍可维持血糖正常。阐明伴随糖尿病发生的肥胖进展机制，将为2型糖尿病的发病机理提供重要线索。因此，我们进一步对五组存在不同程度高血糖的肥胖小鼠的脂肪组织进行基因表达水平检测，最终筛选出88个表达水平与糖尿病严重程度显著相关的基因。该基因集合中包含诸多已知参与信号转导与能量代谢的基因，同时也涵盖了此前未被关联至糖尿病发病过程的基因。本研究数据表明，通常参与脂肪生成（adipogenesis）的基因表达下调与肥胖发生相关，同时我们还进一步筛选出了对2型糖尿病后续发病具有重要作用的基因。