Nadler S T, Stoehr J P, Schueler K L, Tanimoto G, Yandell B S, Attie A D
Departments of Biochemistry, and Statistics and Horticulture, University of Wisconsin, Madison, WI, 53706, USA.
Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11371-6. doi: 10.1073/pnas.97.21.11371.
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型糖尿病密切相关，2型糖尿病是一种常见的糖脂代谢紊乱疾病。虽然脂肪细胞在肥胖中至关重要，但其在糖尿病中的作用直到最近才受到重视。我们通过使用DNA微阵列进行研究，以鉴定瘦小鼠、肥胖小鼠和肥胖糖尿病小鼠脂肪组织中基因表达的差异。分析了超过11,000个转录本的表达水平，其中214个转录本在瘦小鼠和肥胖小鼠之间表现出显著差异。令人惊讶的是，通常与脂肪细胞分化相关的基因在肥胖中表达下调。并非所有肥胖个体都会患糖尿病；许多人尽管肥胖严重，但血糖仍保持正常。了解肥胖伴发糖尿病的转变过程将为2型糖尿病的发病机制提供重要线索。因此，我们检测了五组不同程度高血糖肥胖小鼠脂肪组织中的基因表达水平，并鉴定出88个基因，其表达与糖尿病严重程度密切相关。这组基因包括许多已知参与信号转导和能量代谢的基因，以及以前未在糖尿病背景下研究过的基因。我们的数据表明，正常参与脂肪生成的基因表达降低与肥胖有关，并且我们进一步鉴定了对2型糖尿病后续发展重要的基因。
