Letter abstract

Nature Medicine 15, 442 - 446 (2009)
Published online: 15 March 2009 | doi:10.1038/nm.1937

Deficiency of the intestinal enzyme acyl CoA:monoacylglycerol acyltransferase-2 protects mice from metabolic disorders induced by high-fat feeding

Chi-Liang Eric Yen1,2,5, Mei-Leng Cheong1, Carrie Grueter1,2, Ping Zhou1, Junya Moriwaki1, Jinny S Wong1, Brian Hubbard3, Stephen Marmor3 & Robert V Farese Jr1,2,4


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 abundant1, 2. 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.

  1. Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA.
  2. Cardiovascular Research Institute, University of California, San Francisco, California, USA.
  3. Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA.
  4. Departments of Medicine, Biochemistry and Biophysics, University of California, San Francisco, California, USA.
  5. Current address: Department of Nutritional Sciences, University of Wisconsin–Madison, Madison, Wisconsin, USA.

Correspondence to: Robert V Farese Jr1,2,4 e-mail: bfarese@gladstone.ucsf.edu


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