MGAT2 deficiency ameliorates high-fat diet-induced obesity and insulin resistance by inhibiting intestinal fat absorption in mice
<p>Abstract</p> <p>Background</p> <p>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 t...
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| Format: | Article |
| Language: | English |
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BMC
2012-06-01
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| Series: | Lipids in Health and Disease |
| Subjects: | |
| Online Access: | http://www.lipidworld.com/content/11/1/75 |
| _version_ | 1811287843702571008 |
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| author | Tsuchida Takuma Fukuda Sayaka Aoyama Hisanori Taniuchi Nobuhiko Ishihara Tomomi Ohashi Noriko Sato Hiroko Wakimoto Koji Shiotani Masaharu Oku Akira |
| author_facet | Tsuchida Takuma Fukuda Sayaka Aoyama Hisanori Taniuchi Nobuhiko Ishihara Tomomi Ohashi Noriko Sato Hiroko Wakimoto Koji Shiotani Masaharu Oku Akira |
| author_sort | Tsuchida Takuma |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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 <it>Mgat2-</it>deficient mice.</p> <p>Results</p> <p>In oral fat tolerance test (OFTT), <it>Mgat2</it>-deficient mice absorbed less fat into the circulation. When maintained on a high-fat diet (HFD), <it>Mgat2</it>-deficient mice were protected from HFD-induced obesity and insulin resistance. Heterozygote (<it>Mgat2</it><sup><it>+/−</it></sup>) mice had an intermediate phenotype between <it>Mgat2</it><sup><it>+/+</it></sup> and <it>Mgat2</it><sup><it>−/−</it></sup> and were partially protected from metabolic disorders. Despite of a decrease in fat absorption in the <it>Mgat2</it>-deficient mice, lipid levels in the feces and small intestine were comparable among the genotypes. Oxygen consumption was increased in the <it>Mgat2</it>-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 <it>Mgat2</it>-deficient mice.</p> <p>Conclusion</p> <p>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.</p> |
| first_indexed | 2024-04-13T03:25:31Z |
| format | Article |
| id | doaj.art-dabc6125f34440a6bf45cbfdcafba067 |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-04-13T03:25:31Z |
| publishDate | 2012-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj.art-dabc6125f34440a6bf45cbfdcafba0672022-12-22T03:04:40ZengBMCLipids in Health and Disease1476-511X2012-06-011117510.1186/1476-511X-11-75MGAT2 deficiency ameliorates high-fat diet-induced obesity and insulin resistance by inhibiting intestinal fat absorption in miceTsuchida TakumaFukuda SayakaAoyama HisanoriTaniuchi NobuhikoIshihara TomomiOhashi NorikoSato HirokoWakimoto KojiShiotani MasaharuOku Akira<p>Abstract</p> <p>Background</p> <p>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 <it>Mgat2-</it>deficient mice.</p> <p>Results</p> <p>In oral fat tolerance test (OFTT), <it>Mgat2</it>-deficient mice absorbed less fat into the circulation. When maintained on a high-fat diet (HFD), <it>Mgat2</it>-deficient mice were protected from HFD-induced obesity and insulin resistance. Heterozygote (<it>Mgat2</it><sup><it>+/−</it></sup>) mice had an intermediate phenotype between <it>Mgat2</it><sup><it>+/+</it></sup> and <it>Mgat2</it><sup><it>−/−</it></sup> and were partially protected from metabolic disorders. Despite of a decrease in fat absorption in the <it>Mgat2</it>-deficient mice, lipid levels in the feces and small intestine were comparable among the genotypes. Oxygen consumption was increased in the <it>Mgat2</it>-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 <it>Mgat2</it>-deficient mice.</p> <p>Conclusion</p> <p>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.</p>http://www.lipidworld.com/content/11/1/75Acyl-coenzyme A:monoacylglycerol acyltransferase (MGAT)ObesityInsulin resistanceTriglycerideEnterocyteFatty acid oxidation |
| spellingShingle | Tsuchida Takuma Fukuda Sayaka Aoyama Hisanori Taniuchi Nobuhiko Ishihara Tomomi Ohashi Noriko Sato Hiroko Wakimoto Koji Shiotani Masaharu Oku Akira MGAT2 deficiency ameliorates high-fat diet-induced obesity and insulin resistance by inhibiting intestinal fat absorption in mice Lipids in Health and Disease Acyl-coenzyme A:monoacylglycerol acyltransferase (MGAT) Obesity Insulin resistance Triglyceride Enterocyte Fatty acid oxidation |
| title | MGAT2 deficiency ameliorates high-fat diet-induced obesity and insulin resistance by inhibiting intestinal fat absorption in mice |
| title_full | MGAT2 deficiency ameliorates high-fat diet-induced obesity and insulin resistance by inhibiting intestinal fat absorption in mice |
| title_fullStr | MGAT2 deficiency ameliorates high-fat diet-induced obesity and insulin resistance by inhibiting intestinal fat absorption in mice |
| title_full_unstemmed | MGAT2 deficiency ameliorates high-fat diet-induced obesity and insulin resistance by inhibiting intestinal fat absorption in mice |
| title_short | MGAT2 deficiency ameliorates high-fat diet-induced obesity and insulin resistance by inhibiting intestinal fat absorption in mice |
| title_sort | mgat2 deficiency ameliorates high fat diet induced obesity and insulin resistance by inhibiting intestinal fat absorption in mice |
| topic | Acyl-coenzyme A:monoacylglycerol acyltransferase (MGAT) Obesity Insulin resistance Triglyceride Enterocyte Fatty acid oxidation |
| url | http://www.lipidworld.com/content/11/1/75 |
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