Intestine-specific deletion of acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2 protects mice from diet-induced obesity and glucose intolerance.
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 tissue 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 (Mogat2(IKO)). We found that, like Mogat2(-/-) mice, Mogat2(IKO) 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. Mogat2(IKO) mice increased energy expenditure although 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 extraintestinal tissues may also modulate energy metabolism.
From the Department of Nutritional Sciences, University of Wisconsin, Madison, Wisconsin 53706.
David W
DW
Nelson
From the Department of Nutritional Sciences, University of Wisconsin, Madison, Wisconsin 53706.
Yu
Y
Gao
From the Department of Nutritional Sciences, University of Wisconsin, Madison, Wisconsin 53706.
Mei-I
MI
Yen
From the Department of Nutritional Sciences, University of Wisconsin, Madison, Wisconsin 53706 yen@nutrisci.wisc.edu.
Chi-Liang Eric
CL
Yen
D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D004435:Eating / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005234:Fatty Liver / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D017353:Gene Deletion; D018149:Glucose Intolerance / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D006937:Hypercholesterolemia / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D007408:Intestinal Absorption / Q000187:drug effects / Q000235:genetics; D007422:Intestines / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control
D004041:Dietary Fats; D017351:N-Acetylglucosaminyltransferases; C063313:alpha-1,6-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase
Diacylglycerol; Diet; Energy Metabolism; Lipid Absorption; Triacylglycerol