酰基辅酶 A：二酰基甘油酰基转移酶 1 在肠内的特异性表达可逆转 Dgat1-/- 小鼠对饮食诱导的肝脂肪变性和肥胖的抵抗力。
Intestine-specific expression of acyl CoA:diacylglycerol acyltransferase 1 reverses resistance to diet-induced hepatic steatosis and obesity in Dgat1-/- mice.
机构信息
Department of Foods and Nutrition, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
出版信息
J Lipid Res. 2010 Jul;51(7):1770-80. doi: 10.1194/jlr.M002311. Epub 2010 Feb 10.
Abstract
Mice deficient in acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in triacylglycerol (TG) biosynthesis, are resistant to high-fat (HF) diet-induced hepatic steatosis and obesity. DGAT1-deficient (Dgat1-/-) mice have no defect in quantitative absorption of dietary fat; however, they have abnormally high levels of TG stored in the cytoplasm of enterocytes, and they have a reduced postprandial triglyceridemic response. We generated mice expressing DGAT1 only in the intestine (Dgat1IntONLY) to determine whether this phenotype contributes to resistance to HF diet-induced hepatic steatosis and obesity in Dgat1-/- mice. Despite lacking DGAT1 in liver and adipose tissue, we found that Dgat1IntONLY mice are not resistant to HF diet-induced hepatic steatosis or obesity. The results presented demonstrate that intestinal DGAT1 stimulates dietary fat secretion out of enterocytes and that altering this cellular function alters the fate of dietary fat in specific tissues.
摘要
缺乏酰基辅酶 A：二酰基甘油酰基转移酶 1（DGAT1）的小鼠，一种三酰基甘油（TG）生物合成的关键酶，对高脂肪（HF）饮食诱导的肝脂肪变性和肥胖有抗性。DGAT1 缺陷（Dgat1-/-）小鼠在定量吸收膳食脂肪方面没有缺陷；然而，它们的肠细胞细胞质中储存的 TG 水平异常高，餐后甘油三酯血症反应降低。我们生成了仅在肠道中表达 DGAT1 的小鼠（Dgat1IntONLY），以确定这种表型是否有助于 Dgat1-/- 小鼠抵抗 HF 饮食诱导的肝脂肪变性和肥胖。尽管在肝脏和脂肪组织中缺乏 DGAT1，我们发现 Dgat1IntONLY 小鼠不易发生 HF 饮食诱导的肝脂肪变性或肥胖。所呈现的结果表明，肠道 DGAT1 刺激肠细胞中膳食脂肪的分泌，并且改变这种细胞功能改变了膳食脂肪在特定组织中的命运。
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本文引用的文献
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Specific role for acyl CoA:Diacylglycerol acyltransferase 1 (Dgat1) in hepatic steatosis due to exogenous fatty acids.酰基辅酶A：二酰甘油酰基转移酶1（Dgat1）在外源性脂肪酸导致的肝脂肪变性中的特定作用。
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