A predominant role of acyl-CoA: Monoacylglycerol acyltransferase-2 in dietary fat absorption implicated by tissue distribution, subcellular localization, and up-regulation by high fat diet
A predominant role of acyl-CoA: Monoacylglycerol acyltransferase-2 in dietary fat absorption implicated by tissue distribution, subcellular localization, and up-regulation by high fat diet
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DOI：
10.1074/jbc.m313272200
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发表时间：
2004-04-30
影响因子：
4.8
通讯作者：
Shi, YG
中科院分区：
文献类型：
--
作者：
Cao, JS;Hawkins, E;Shi, YG
酰基辅酶A：单酰基甘油酰基转移酶-2（MGAT 2）催化二酰基甘油的合成，并且在mRNA水平的组织分布上不同于MGAT 1和MGAT 3。除小肠外，MGAT 2 mRNA还在人肝脏、下胃肠道和小鼠肾脏中高水平表达，但尚未研究这种表达的生理意义。利用亲和纯化的抗体，本研究调查了小鼠MGAT 2蛋白沿着肠道的表达，确定其亚细胞定位，并研究了其通过饮食和在db/db小鼠中的调节。结果表明，小肠中MGAT 2以近端至远端的梯度高水平表达，其与MGAT酶活性和脂肪吸收模式均良好相关。相比之下，MGAT 2蛋白在消化道的其他部分（包括胃、盲肠、结肠和直肠）或其他小鼠组织（如肾、肝和脂肪细胞）中检测不到。免疫组织学研究提供了直接的证据，该酶不仅在绒毛中表达，而且在小肠的隐窝区域中表达，这表明MGAT 2表达发生在肠上皮细胞成熟之前。MGAT 2在MGAT 2转染的COS-7和Caco-2细胞中定位于内质网（ER）中，表明ER是膳食脂肪再合成的主要位点。在db/db小鼠中，MGAT 2表达似乎不受糖尿病的影响，然而，总肠道MGAT活性显著增强。最后，在喂食高脂肪饮食的小鼠中观察到MGAT 2蛋白表达和MGAT活性的上调，暗示MGAT 2在饮食诱导的肥胖中的作用。总之，我们的数据表明MGAT 2在膳食脂肪吸收中起主导作用。
Acyl-CoA: monoacylglycerol acyltransferase-2 (MGAT2) catalyzes the synthesis of diacylglycerol and differs from the MGAT1 and MGAT3 in tissue distribution at the mRNA level. In addition to the small intestine, MGAT2 mRNA is also expressed at high levels in human liver, the lower gastrointestinal tract, and the mouse kidney, but the physiological significance of such expression has not yet been studied. Using an affinity-purified antibody, the present study investigated the expression of murine MGAT2 protein along the intestinal tract, determined its subcellular localization, and studied its regulation by diet and in db/db mouse. Results demonstrate a high level of MGAT2 expression in the small intestine in a proximal-to-distal gradient that correlated well with both MGAT enzyme activity and fat absorption pattern. In contrast, MGAT2 protein was not detectable in other sections of the digestive tract, including stomach, cecum, colon, and rectum, or other mouse tissues such as kidney, liver, and adipocytes. Immunohistological studies provided direct evidence that the enzyme is expressed not only in the villi, but also in the crypt regions of the small intestine, which suggests that MGAT2 expression occurs prior to the maturation of enterocytes. MGAT2 is localized in the endoplasmic reticulum (ER) in both MGAT2-transfected COS-7 and Caco-2 cells, indicating that the ER is the primary site for dietary fat re-synthesis. MGAT2 expression appeared not to be affected by diabetes in the db/db mouse, however, the total intestinal MGAT activity was significantly enhanced. Finally, an up-regulation of both MGAT2 protein expression and MGAT activity was observed in mice fed a high fat diet, implicating a role of MGAT2 in diet-induced obesity. Taken together, our data suggest a predominant role of MGAT2 in dietary fat absorption.