MGAT2 deficiency ameliorates high-fat diet-induced obesity and insulin resistance by inhibiting intestinal fat absorption in mice

Lipids in Health and Disease

Akira Oku²  Masaharu Shiotani²  Koji Wakimoto¹  Hiroko Sato⁴  Noriko Ohashi²  Tomomi Ishihara²  Nobuhiko Taniuchi²  Hisanori Aoyama³  Sayaka Fukuda²  Takuma Tsuchida² 

[1] Target Discovery and Biomarker Research Department, Advanced Medical Research Laboratories, Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan;Department I, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama, 335-8505, Japan;Discovery molecular pharmacology Department, Discovery Screening Center, Research Division, Mitsubishi Tanabe Pharma Corporation, Saitama, Japan;Safety Department II, Safety Research Laboratory, Research Division, Mitsubishi Tanabe Pharma Corporation, Chiba, Japan

关键词: Fatty acid oxidation;    Enterocyte;    Triglyceride;    Insulin resistance;    Obesity;    Acyl-coenzyme A:monoacylglycerol acyltransferase (MGAT);   

Others  :  1160276
DOI  :  10.1186/1476-511X-11-75

 received in 2012-03-13, accepted in 2012-04-27,  发布年份 2012

【 摘 要 】

Background

Resynthesis of triglycerides in enterocytes of the small intestine plays a critical role in the absorption of dietary fat. Acyl-CoA:monoacylglycerol acyltransferase-2 (MGAT2) is highly expressed in the small intestine and catalyzes the synthesis of diacylglycerol from monoacylglycerol and acyl-CoA. To determine the physiological importance of MGAT2 in metabolic disorders and lipid metabolism in the small intestine, we constructed and analyzed Mgat2-deficient mice.

Results

In oral fat tolerance test (OFTT), Mgat2-deficient mice absorbed less fat into the circulation. When maintained on a high-fat diet (HFD), Mgat2-deficient mice were protected from HFD-induced obesity and insulin resistance. Heterozygote (Mgat2^+/−) mice had an intermediate phenotype between Mgat2^+/+ and Mgat2^−/− and were partially protected from metabolic disorders. Despite of a decrease in fat absorption in the Mgat2-deficient mice, lipid levels in the feces and small intestine were comparable among the genotypes. Oxygen consumption was increased in the Mgat2-deficient mice when maintained on an HFD. A prominent upregulation of the genes involved in fatty acid oxidation was observed in the duodenum but not in the liver of the Mgat2-deficient mice.

Conclusion

These results suggest that MGAT2 has a pivotal role in lipid metabolism in the small intestine, and the inhibition of MGAT2 activity may be a promising strategy for the treatment of obesity-related metabolic disorders.

【 授权许可】

   
2012 Tsuchida et al.; licensee BioMed Central Ltd.

【 图 表 】

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