Intestine-specific deletion of Acyl CoA:monoacylglycerol acyltransferase (MGAT)2 protects mice from diet-induced obesity and glucose intolerance [Lipids]

May 1st, 2014 by Nelson, D. W., Gao, Y., Yen, M.-I., Yen, C.-L. E.

The absorption of dietary fat involves the re-esterification of digested triacylglycerol in the enterocytes, a process catalyzed by acyl CoA:monoacylglycerol acyltransferase (MGAT) 2. Mice without a functional gene encoding MGAT2 (Mogat2-/-) are protected from diet-induced obesity. Surprisingly, these mice absorb normal amounts of dietary fat but increase their energy expenditure. MGAT2 is expressed in tissues besides intestine, including adipose in both mice and humans. To test the hypothesis that intestinal MGAT2 regulates systemic energy balance, we generated and characterized mice deficient in MGAT2 specifically in the small intestine (Mogat2IKO). We found that, like Mogat2-/- mice, Mogat2IKO mice also showed a delay in fat absorption, a decrease in food intake, and a propensity to use fatty acids as fuel when first exposed to a high-fat diet. Mogat2IKO mice increased energy expenditure, though to a lesser degree than Mogat2-/- mice, and were protected against diet-induced weight gain 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 and may be a feasible intervention target. In addition, they suggest that MGAT activity in extra-intestinal tissues may also modulate energy metabolism.
  • Posted in Journal of Biological Chemistry, Publications
  • Comments Off on Intestine-specific deletion of Acyl CoA:monoacylglycerol acyltransferase (MGAT)2 protects mice from diet-induced obesity and glucose intolerance [Lipids]