Department of Medicine, University of California, San Francisco, CA 94103, USA.
Nutr Metab (Lond). 2006 Jan 31;3:10. doi: 10.1186/1743-7075-3-10.
Although the ability to make triglycerides is essential for normal physiology, excess accumulation of triglycerides results in obesity and is associated with insulin resistance. Inhibition of triglyceride synthesis, therefore, may represent a feasible strategy for the treatment of obesity and type 2 diabetes. Acyl CoA:diacylglycerol acyltransferase 1 (DGAT1) is one of two DGAT enzymes that catalyze the final reaction in the known pathways of mammalian triglyceride synthesis. Mice lacking DGAT1 have increased energy expenditure and insulin sensitivity and are protected against diet-induced obesity and glucose intolerance. These metabolic effects of DGAT1 deficiency result in part from the altered secretion of adipocyte-derived factors. Studies of DGAT1-deficient mice have helped to provide insights into the mechanisms by which cellular lipid metabolism modulates systemic carbohydrate and insulin metabolism, and a better understanding of how DGAT1 deficiency enhances energy expenditure and insulin sensitivity may identify additional targets or strategies for the treatment of obesity and type 2 diabetes.
尽管合成甘油三酯的能力对于正常生理机能至关重要，但甘油三酯的过度积累会导致肥胖，并与胰岛素抵抗有关。因此，抑制甘油三酯的合成可能代表了治疗肥胖和 2 型糖尿病的一种可行策略。酰基辅酶 A：二酰基甘油酰基转移酶 1（DGAT1）是催化哺乳动物甘油三酯合成已知途径中最后一个反应的两种 DGAT 酶之一。缺乏 DGAT1 的小鼠能量消耗增加，胰岛素敏感性增强，并且可以预防饮食诱导的肥胖和葡萄糖不耐受。DGAT1 缺乏的这些代谢作用部分归因于脂肪细胞衍生因子分泌的改变。对 DGAT1 缺乏的小鼠的研究有助于深入了解细胞脂质代谢如何调节全身碳水化合物和胰岛素代谢的机制，并且更好地了解 DGAT1 缺乏如何增强能量消耗和胰岛素敏感性可能会确定治疗肥胖和 2 型糖尿病的其他靶点或策略。
