《生命科学》 2010, 22(2): 173-178

潜在的防治肥胖及糖尿病靶标——DGAT

闫桂蕊，张小东，朱维良，王贺瑶^*

(中国科学院上海药物研究所，上海201203）

摘　要：

摘 要：二酰基甘油酰基转移酶(DGAT)是甘油三酯(TG)合成的关键酶，催化TG合成的最后一步。DGAT有两种亚型：DGAT1和DGAT2。DGAT1缺陷的小鼠对胰岛素和瘦素的敏感性增加且可以抵抗饮食诱导的肥胖；DGAT2功能下调可明显降低肥胖小鼠肝脏TG含量，改善脂肪肝的形成。DGAT抑制剂可改善动物模型的高脂血症和脂肪肝。因此，DGAT有可能成为防治肥胖、糖尿病等代谢性疾病的新的药物靶标。该文详细阐述了DGAT的生理功能研究及其抑制剂的研究进展。
关键词：DGAT；肥胖；糖尿病；脂肪肝；靶标

DGAT: a new target for prevention and treatment of obesity and diabetes

YAN Gui-rui， ZHANG Xiao-dong， ZHU Wei-liang， WANG He-yao^*

(Shanghai Institute of Materia Media， Chinese Academy of Sciences， Shanghai 201213， China)

Abstract:

Abstract：Acly CoA: diacylglycerol acyltransferase (DGAT) is a key enzyme that catalyzes the final reaction of triacylgycerol (TG) synthesis. DGAT has two subtypes including DGAT1 and DGAT2. DGAT1 deficiency increased the sensitivity of tested mice to both insulin and leptin， and protected them against diet-induced obesity. Reducing DGAT2抯 expression in liver caused a marked reduction in hepatic TG content and improved hepatic steatosis of obese mice. DGAT inhibitors ameliorated hyperlipoidemia and fatty liver in vivo. Therefore， DGATs have been viewed as potential therapeutic targets for prevention and treatment of obesity and diabetes. The functions and inhibitors of DGAT are discussed in this review.
Key words: DGAT; obesity; fatty liver; diabetes; target