Chen Hubert C, Farese Robert V
Department of Medical Sciences, Amgen Inc, Thousand Oaks, USA.
Arterioscler Thromb Vasc Biol. 2005 Mar;25(3):482-6. doi: 10.1161/01.ATV.0000151874.81059.ad. Epub 2004 Nov 29.
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.
由于合成甘油三酯的能力对于脂肪组织的积累至关重要，抑制甘油三酯合成可能会改善肥胖及其相关的医学后果。酰基辅酶A（CoA）：二酰甘油酰基转移酶1（DGAT1）是催化哺乳动物甘油三酯合成已知途径中最终反应的2种DGAT酶之一。缺乏DGAT1的小鼠对肥胖具有抗性，并且对胰岛素和瘦素的敏感性增加。DGAT1缺陷型小鼠对饮食诱导的肝脂肪变性也具有抗性。DGAT1缺乏对能量和葡萄糖代谢的影响部分源于脂肪细胞衍生因子分泌的改变。尽管完全缺乏DGAT1会导致脱发并损害乳腺发育，但在部分缺乏DGAT1的小鼠中未观察到这些异常。这些发现表明，对DGAT1进行药物抑制可能是治疗人类肥胖和2型糖尿病的可行策略。
