Variation in the adiponutrin gene influences its expression and associates with obesity
Variation in the adiponutrin gene influences its expression and associates with obesity
复制标题
DOI：
10.2337/diabetes.55.03.06.db05-1075
复制
发表时间：
2006-03-01
期刊：
影响因子：
7.7
通讯作者：
Ridderstråle, M
中科院分区：
文献类型：
--
作者：
Johansson, LE;Hoffstedt, J;Ridderstråle, M
脂降素是最近发现的三种脂肪细胞脂肪酶之一。令人惊讶的是，这些蛋白质还保留转酰基酶活性，这是迄今为止未知的脂肪细胞中三酰甘油合成途径。这可能使它们参与合成代谢和分解代谢过程。脂肪素基因（ADPN）在禁食时下调，在进食时上调，提示其在脂肪生成中起作用。在人类脂肪细胞中的实验证实，该基因在胰岛素的作用下以葡萄糖依赖的方式上调。肥胖受试者皮下和内脏腹部脂肪组织ADPN mRNA水平升高。内脏ADPN mRNA表达与胰岛素敏感性（空腹胰岛素和体内平衡模型评估）相关。我们还研究了ADPN的遗传变异及其与肥胖、脂肪分解和mRNA表达的关系。两个ADPN多态性显示与肥胖有关。肥胖相关变异的携带者显示脂肪组织ADPN mRNA水平的增加较少，基础脂肪分解增加。我们的研究结果表明，胰岛素抵抗和/或肥胖相关ADPN等位基因携带者的肥胖受试者无法上调该基因，而脂降素的上调可能是对协调能量过剩的适当反应。
Adiponutrin is one of three recently identified adipocyte lipases. Surprisingly, these proteins also retain transacylase activity, a hitherto unknown pathway of triacylglycerol synthesis in the adipocytes. This may enable them to participate in both anabolic and catabolic processes. The adiponutrin gene (ADPN) is downregulated by fasting and upregulated by refeeding, suggesting a role in lipogenesis. Experiments in human adipocytes confirmed that the gene is upregulated in response to insulin in a glucose-dependent fashion. Obese subjects had increased levels of subcutaneous and visceral abdominal adipose tissue ADPN mRNA. Visceral ADPN mRNA expression was correlated to measures of insulin sensitivity (fasting insulin and homeostasis model assessment). We also studied genetic variation in ADPN and its relation to obesity, lipolysis, and mRNA expression. Two ADPN polymorphisms showed association with obesity. Carriers of the obesity-associated variants showed a lesser increase in the levels of adipose tissue ADPN mRNA and an increased basal lipolysis. Our results suggest that obese subjects that are insulin resistant and/or carriers of the obesity-associated ADPN alleles fail to upregulate the gene and that upregulation of adiponutrin may be an appropriate response to orchestrate energy excess.