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Intestine‐specific inactivation of acyl CoA: monoacylglycerol acyltransferase 2 protects mice from diet‐induced obesity (822.12)
Author(s) -
Yen ChiLiang Eric,
Nelson David,
Gao Yu,
Yen MeiI
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.822.12
Subject(s) - steatosis , endocrinology , medicine , monoacylglycerol lipase , small intestine , acyl coa , adipose tissue , lipid metabolism , metabolism , fatty liver , lipogenesis , biology , chemistry , enzyme , biochemistry , endocannabinoid system , receptor , disease
Acyl: CoA: monoacylglycerol acyltransferase (MGAT)2 catalyzes the re‐esterification of triacylglycerol in the enterocytes, a step required for fat absorption. Mice without functional MGAT2 enzymes (Mogat2‐/‐) are protected from diet‐induced obesity but, surprisingly, absorb normal amount of dietary fat and exhibit increased energy expenditure. MGAT2 is expressed in tissues besides intestine, including the kidney and adipose tissues in both mice and humans. To test the hypothesis that intestinal MGAT2 regulates systemic energy balance, in this study, we generated and characterized mice deficient in MGAT2 exclusively in the small intestine (Mogat2IKO). We found that, like Mogat2‐/‐ mice, Mogat2IKO mice showed delayed in fat absorption, a transient decrease in food intake when first exposed to a high‐fat diet, and a propensity to use fatty acids as fuel. Though to a lesser extent than Mogat2‐/‐ mice, Mogat2IKO mice also exhibited a persistent increase in energy expenditure and are protected against diet‐induced weight gain, excessive expansion of body fat, and associated comorbidities, including hepatic steatosis, hypercholesterolemia, and glucose intolerance. These findings illustrate that intestinal lipid metabolism plays a crucial role in the regulation of systemic energy balance. In addition, they also suggest that MGAT activity in tissues beside intestine may also contribute to energy metabolism. Grant Funding Source : Supported by NIH DK088210