Deficiency of the intestinal enzyme acyl CoA:monoacylglycerol acyltransferase-2 protects mice from metabolic disorders induced by high-fat feeding.
Animals are remarkably efficient in absorbing dietary fat and assimilating this energy-dense nutrient into the white adipose tissue (WAT) for storage. Although this metabolic efficiency may confer an advantage in times of calorie deprivation, it contributes to obesity and associated metabolic disorders when dietary fat is abundant. Here we show that the intestinal lipid synthesis enzyme acyl CoA:monoacylglycerol acyltransferase-2 (MGAT2) has a crucial role in the assimilation of dietary fat and the accretion of body fat in mice. Mice lacking MGAT2 have a normal phenotype on a low-fat diet. However, on a high-fat diet, MGAT2-deficient mice are protected against developing obesity, glucose intolerance, hypercholesterolemia and fatty livers. Caloric intake is normal in MGAT2-deficient mice, and dietary fat is absorbed fully. However, entry of dietary fat into the circulation occurs at a reduced rate. This altered kinetics of fat absorption apparently results in more partitioning of dietary fat toward energy dissipation rather than toward storage in the WAT. Thus, our studies identify MGAT2 as a key determinant of energy metabolism in response to dietary fat and suggest that the inhibition of this enzyme may prove to be a useful strategy for treating obesity and other metabolic diseases associated with excessive fat intake.
Yen
Chi-Liang Eric
CL
Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA.
Cheong
Mei-Leng
ML
Grueter
Carrie
C
Zhou
Ping
P
Moriwaki
Junya
J
Wong
Jinny S
JS
Hubbard
Brian
B
Marmor
Stephen
S
Farese
Robert V
RV
D000217:Acyltransferases / Q000172:deficiency*; D000273:Adipose Tissue / Q000187:drug effects / Q000503:physiopathology; D000818:Animals; D001831:Body Temperature; D001835:Body Weight; D004041:Dietary Fats / Q000009:adverse effects*; D002149:Energy Intake; D004734:Energy Metabolism; D005260:Female; D006128:Growth; D006937:Hypercholesterolemia / Q000517:prevention & control; D008297:Male; D051379:Mice; D009765:Obesity / Q000235:genetics* / Q000517:prevention & control
D004041:Dietary Fats; D000217:Acyltransferases; C021802:2-acylglycerol O-acyltransferase