title: Deficiency of the intestinal enzyme acyl CoA:monoacylglycerol acyltransferase-2 protects mice from metabolic disorders induced by high-fat feeding.
abstract: 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.
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA.
authors.forename: Chi-Liang Eric
authors.initials: CL
authors.lastname: Yen
authors.forename: Mei-Leng
authors.initials: ML
authors.lastname: Cheong
authors.forename: Carrie
authors.initials: C
authors.lastname: Grueter
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Junya
authors.initials: J
authors.lastname: Moriwaki
authors.forename: Jinny S
authors.initials: JS
authors.lastname: Wong
authors.forename: Brian
authors.initials: B
authors.lastname: Hubbard
authors.forename: Stephen
authors.initials: S
authors.lastname: Marmor
authors.forename: Robert V
authors.initials: RV
authors.lastname: Farese
mesh_terms: 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
chemical_list: D004041:Dietary Fats; D000217:Acyltransferases; C021802:2-acylglycerol O-acyltransferase