Intestine-specific expression of MOGAT2 partially restores metabolic efficiency in Mogat2-deficient mice
Intestine-specific expression of MOGAT2 partially restores metabolic efficiency in Mogat2-deficient mice
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DOI：
10.1194/jlr.m035493
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发表时间：
2013-06-01
影响因子：
6.5
通讯作者：
Yen, Chi-Liang Eric
中科院分区：
文献类型：
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作者：
Gao, Yu;Nelson, David W.;Yen, Chi-Liang Eric
酰基辅酶A：单酰基甘油酰基转移酶（MGAT）催化三酰基甘油的再合成，这是膳食脂肪吸收的关键步骤。缺乏Mogat 2基因的小鼠，其编码在小肠中高度表达的MGAT，对肥胖和由高脂肪喂养引起的其他代谢紊乱具有抵抗力。有趣的是，这些Mogat 2（-/-）小鼠吸收正常量的膳食脂肪，但表现出脂肪吸收率降低、能量消耗增加、呼吸交换率降低和代谢效率受损。MGAT 2在肠外组织中表达。为了检验肠道MGAT 2增强代谢效率并促进代谢燃料储存的假设，我们将由精氨酸特异性绒毛蛋白启动子驱动的人MOGAT 2基因引入Mogat 2（-/-）小鼠。我们发现MOGAT 2在肠道中的表达增加了肠道MGAT活性，恢复了脂肪吸收率，部分纠正了能量消耗，并促进了高脂喂养后的体重增加。然而，呼吸交换率的变化没有恢复，代谢效率和体重增加的恢复是不完全的。这些数据表明，肠中的MGAT 2在提高代谢效率方面起着不可或缺的作用，但也提高了其他组织中的MGAT 2可能有助于调节能量代谢的可能性。
Acyl CoA:monoacylglycerol acyltransferase (MGAT) catalyzes the resynthesis of triacylglycerol, a crucial step in the absorption of dietary fat. Mice lacking the gene Mogat2, which codes for an MGAT highly expressed in the small intestine, are resistant to obesity and other metabolic disorders induced by high-fat feeding. Interestingly, these Mogat2(-/-) mice absorb normal amounts of dietary fat but exhibit a reduced rate of fat absorption, increased energy expenditure, decreased respiratory exchange ratio, and impaired metabolic efficiency. MGAT2 is expressed in tissues besides intestine. To test the hypothesis that intestinal MGAT2 enhances metabolic efficiency and promotes the storage of metabolic fuels, we introduced the human MOGAT2 gene driven by the intestine-specific villin promoter into Mogat2(-/-) mice. We found that the expression of MOGAT2 in the intestine increased intestinal MGAT activity, restored fat absorption rate, partially corrected energy expenditure, and promoted weight gain upon high-fat feeding. However, the changes in respiratory exchange ratio were not reverted, and the recoveries in metabolic efficiency and weight gain were incomplete. These data indicate that MGAT2 in the intestine plays an indispensable role in enhancing metabolic efficiency but also raise the possibility that MGAT2 in other tissues may contribute to the regulation of energy metabolism.