DGAT1 is not essential for intestinal triacylglycerol absorption or chylomicron synthesis
DGAT1 is not essential for intestinal triacylglycerol absorption or chylomicron synthesis
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DOI：
10.1074/jbc.m202013200
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发表时间：
2002-07-12
影响因子：
4.8
通讯作者：
Farese, RV
中科院分区：
文献类型：
--
作者：
Buhman, KK;Smith, SJ;Farese, RV
膳食中的甘油三酯是动物的主要能量来源。膳食中甘油三酯的吸收包括其在肠腔内水解为游离脂肪酸和单甘油三酯，这些产物被肠细胞吸收，三甘油三酯的再合成，以及新合成的甘油三酯并入新生乳糜微粒分泌。在肠细胞中，三酰基甘油合成的最后一步被认为主要是通过酰基辅酶a的作用催化的：二酰基甘油酰基转移酶（DGAT）酶。在本研究中，我们分析了Dgat1缺陷（Dgat1(-/-)）小鼠肠道中甘油三酯的吸收和乳糜微粒的合成和分泌。令人惊讶的是，即使在喂食高脂肪食物的小鼠中，DGAT1也不是定量饮食中甘油三酯吸收或乳糜微粒合成所必需的。然而，长期喂食高脂肪饮食后，Dgat1（-/-）小鼠吸收后乳糜微粒血症（高脂肪刺激后1小时）减少，并在肠细胞细胞质中积累中性脂滴。这些结果表明，Dgat1（-/-）小鼠的甘油三酯吸收率降低。对Dgat1（-/-）小鼠肠道的分析显示，DGAT2和二酰基甘油转酰基酶具有活性，这两种酶催化三酰基甘油合成，显然有助于弥补Dgat1的缺失。我们的研究结果表明，肠道中三酰甘油合成的多种机制促进了三酰甘油的吸收。
Dietary triacylglycerols are a major source of energy for animals. The absorption of dietary triacylglycerols involves their hydrolysis to free fatty acids and monoacylglycerols in the intestinal lumen, the uptake of these products into enterocytes, the resynthesis of triacylgylcerols, and the incorporation of newly synthesized triacylglycerols into nascent chylomicrons for secretion. In enterocytes, the final step in triacylglycerol synthesis is believed to be catalyzed primarily through the actions of acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. In this study, we analyzed intestinal triacylglycerol absorption and chylomicron synthesis and secretion in DGAT1-deficient (Dgat1(-/-)) mice. Surprisingly, DGAT1 was not essential for quantitative dietary triacylglycerol absorption, even in mice fed a high fat diet, or for the synthesis of chylomicrons. However, Dgat1(-/-)mice had reduced postabsorptive chylomicronemia (1 h after a high fat challenge) and accumulated neutrallipid droplets in the cytoplasm of enterocytes when chronically fed a high fat diet. These results suggest a reduced rate of triacylglycerol absorption in Dgat1(-/-)mice. Analysis of intestine from Dgat1(-/-) mice revealed activity for two other enzymes, DGAT2 and diacylglycerol transacylase, that catalyze triacylglycerol synthesis and apparently help to compensate for the absence of DGAT1. Our findings indicate that multiple mechanisms for triacylglycerol synthesis in the intestine facilitate triacylglycerol absorption.