Inhibition of triglyceride synthesis as a treatment strategy for obesity - Lessons from DGAT1-deficient mice
Inhibition of triglyceride synthesis as a treatment strategy for obesity - Lessons from DGAT1-deficient mice
复制标题
DOI：
10.1161/01.atv.0000151874.81059.ad
复制
发表时间：
2005-03-01
影响因子：
8.7
通讯作者：
Farese, RV
中科院分区：
文献类型：
--
作者：
Chen, HC;Farese, RV
因为制造甘油三酯的能力对于脂肪组织的积累是必不可少的，抑制甘油三酯的合成可能会改善肥胖及其相关的医学后果。酰基辅酶A (CoA)：二酰基甘油酰基转移酶1 （DGAT1）是在已知的哺乳动物甘油三酯合成途径中催化最终反应的2种DGAT酶之一。缺乏DGAT1的小鼠对肥胖有抵抗力，对胰岛素和瘦素的敏感性增加。dgat1缺陷小鼠也对饮食诱导的肝脂肪变性有抵抗力。DGAT1缺乏对能量和葡萄糖代谢的影响部分是由于脂肪细胞衍生因子的分泌改变。尽管完全DGAT1缺乏会导致脱发并损害乳腺的发育，但在部分DGAT1缺乏的小鼠中未观察到这些异常。这些发现表明，药物抑制DGAT1可能是治疗人类肥胖和2型糖尿病的可行策略。
Because the ability to make triglycerides is essential for the accumulation of adipose tissue, inhibition of triglyceride synthesis may ameliorate obesity and its related medical consequences. Acyl coenzyme A (CoA): diacylglycerol acyltransferase 1 (DGAT1) is 1 of 2 DGAT enzymes that catalyze the final reaction in the known pathways of mammalian triglyceride synthesis. Mice lacking DGAT1 are resistant to obesity and have increased sensitivity to insulin and leptin. DGAT1-deficient mice are also resistant to diet-induced hepatic steatosis. The effects of DGAT1 deficiency on energy and glucose metabolism result in part from the altered secretion of adipocyte-derived factors. Although complete DGAT1 deficiency causes alopecia and impairs development of the mammary gland, these abnormalities are not observed in mice with partial DGAT1 deficiency. These findings suggest that pharmacological inhibition of DGAT1 may be a feasible therapeutic strategy for human obesity and type 2 diabetes.