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J. Biol. Chem., Vol. 279, Issue 12, 11767-11776, March 19, 2004
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Lipopenia and Skin Barrier Abnormalities in DGAT2-deficient Mice*
¶¶
From the
Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141-1900, the Cardiovascular Research Institute and Departments of **Dermatology and Medicine, University of California, San Francisco, California 94143, the Departments of Medicine and ||Dermatology and Medical Service, Veterans Affairs Medical Center, San Francisco, California 94121, and ¶Lipomics Technologies, West Sacramento, California 95691
The synthesis of triglycerides is catalyzed by two known acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. Although they catalyze the same biochemical reaction, these enzymes share no sequence homology, and their relative functions are poorly understood. Gene knockout studies in mice have revealed that DGAT1 contributes to triglyceride synthesis in tissues and plays an important role in regulating energy metabolism but is not essential for life. Here we show that DGAT2 plays a fundamental role in mammalian triglyceride synthesis and is required for survival. DGAT2-deficient (Dgat2-/-) mice are lipopenic and die soon after birth, apparently from profound reductions in substrates for energy metabolism and from impaired permeability barrier function in the skin. DGAT1 was unable to compensate for the absence of DGAT2, supporting the hypothesis that the two enzymes play fundamentally different roles in mammalian triglyceride metabolism.
Received for publication, October 6, 2003 , and in revised form, December 10, 2003.
* This work was supported by a postdoctoral fellowship from the Canadian Institutes of Health Research (to S. J. S.) and National Institutes of Health Grant DK56084 (to R. V. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶¶ To whom correspondence should be addressed. E-mail: bfarese{at}gladstone.ucsf.edu.
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