Mogat1 deletion does not ameliorate hepatic steatosis in lipodystrophic (Agpat2-/-) or obese (ob/ob) mice
Mogat1 deletion does not ameliorate hepatic steatosis in lipodystrophic (Agpat2-/-) or obese (ob/ob) mice
复制标题
DOI：
10.1194/jlr.m065896
复制
发表时间：
2016-04-01
影响因子：
6.5
通讯作者：
Garg, Abhimanyu
中科院分区：
文献类型：
--
作者：
Agarwal, Anil K.;Tunison, Katie;Garg, Abhimanyu
减少肝脏中的三酰甘油（TAG）仍然是非酒精性肝脂肪变性的一个挑战。单酰基甘油O-酰基转移酶（MOGAT）酶将单酰基甘油（MAG）转化为二酰基甘油，二酰基甘油是TAG合成的前体，并且参与选定组织（如小肠）中TAG合成的主要途径。MOGAT 1在体外试验中具有MGAT活性，但其在TAG代谢中的生理功能尚不清楚。最近的研究表明MOGAT 1在脂肪营养不良[1-酰基甘油-3-磷酸O-酰基转移酶（Agpat）2（-/-）]和肥胖（ob /ob）小鼠的肝脏脂肪变性中发挥作用。为了测试这一点，我们在Agpat 2（-/-）和ob /ob遗传背景中删除了Mogat 1，以产生Mogat 1（-/-）; Agpat 2（-/-）和Mogat 1（-/-）; ob /ob双敲除（DKO）小鼠。在这里，我们报告说，尽管在任何DKO小鼠模型中缺乏Mogat 1，但我们没有发现16周龄时肝脏TAG的任何减少。此外，血糖（糖尿病）和胰岛素抵抗无可测量的变化。我们的数据表明MOGAT 1在肝脏TAG合成中的作用最小，如果有的话，并且与脂肪代谢障碍和肥胖相关的脂肪变性中的TAG合成独立于MOGAT 1。我们的研究结果表明MOGAT 1可能在体内具有替代功能。
Reducing triacylglycerol (TAG) in the liver continues to pose a challenge in states of nonalcoholic hepatic steatosis. Monoacylglycerol O-acyltransferase (MOGAT) enzymes convert monoacylglycerol (MAG) to diacylglycerol, a precursor for TAG synthesis, and are involved in a major pathway of TAG synthesis in selected tissues, such as small intestine. MOGAT1 possesses MGAT activity in in vitro assays, but its physiological function in TAG metabolism is unknown. Recent studies suggest a role for MOGAT1 in hepatic steatosis in lipodystrophic [1-acylglycerol-3-phosphate O-acyltransferase (Agpat)2(-/-)] and obese (ob /ob) mice. To test this, we deleted Mogat1 in the Agpat2(-/-) and ob /ob genetic background to generate Mogat1(-/-); Agpat2(-/-) and Mogat1(-/-); ob /ob double knockout (DKO) mice. Here we report that, despite the absence of Mogat1 in either DKO mouse model, we did not find any decrease in liver TAG by 16 weeks of age. Additionally, there were no measureable changes in plasma glucose (diabetes) and insulin resistance. Our data indicate a minimal role, if any, of MOGAT1 in liver TAG synthesis, and that TAG synthesis in steatosis associated with lipodystrophy and obesity is independent of MOGAT1. Our findings suggest that MOGAT1 likely has an alternative function in vivo.