Deficiency of MGAT2 increases energy expenditure without high-fat feeding and protects genetically obese mice from excessive weight gain

Acyl CoA:monoacylglycerol acyltransferase 2 (MGAT2) is thought to be crucial for dietary fat absorption. Indeed, mice lacking the enzyme (Mogat2 / ) are resistant to obesity and other metabolic disorders induced by high- fat feeding. However, these mice absorb normal quantities of fat. To explore whether a high level of dietary fat is an essential part of the underlying mechanism(s), we examined metabolic responses of Mogat2 / mice to diets containing varying levels of fat. Mogat2 / mice exhibited 10 15% in- creases in energy expenditure compared with wild-type lit- termates; although high levels of dietary fat exacerbated the effect, this phenotype was expressed even on a fat-free diet. When deprived of food, Mogat2 / mice expended en- ergy and lost weight like wild-type controls. To determine whether MGAT2 defi ciency protects against obesity in the absence of high-fat feeding, we crossed Mogat2 / mice with genetically obese Agouti mice. MGAT2 defi ciency increased energy expenditure and prevented these mice from gaining excess weight. Our results suggest that MGAT2 modulates energy expenditure through multiple mechanisms, includ- ing one independent of dietary fat; these fi ndings also raise the prospect of inhibiting MGAT2 as a strategy for combat- ing obesity and related metabolic disorders resulting from excessive calorie intake. — Nelson, D. W., Y. Gao, N. M. Spencer, T. Banh, and C-L. E. Yen. Defi ciency of MGAT2 increases energy expenditure without high-fat feeding and protects genetically obese mice from excessive weight gain. J. Lipid Res . 2011. 52: 1723-1732.