Lipopenia and skin barrier abnormalities in DGAT2-deficient mice.
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.
Stone
Scot J
SJ
Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141-1900, USA.
Myers
Heather M
HM
Watkins
Steven M
SM
Brown
Barbara E
BE
Feingold
Kenneth R
KR
Elias
Peter M
PM
Farese
Robert V
RV
D000217:Acyltransferases / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D051048:Diacylglycerol O-Acyltransferase; D006706:Homeostasis; D051379:Mice; D051381:Rats; D012868:Skin Abnormalities / Q000235:genetics*; D014280:Triglycerides / Q000096:biosynthesis / Q000378:metabolism*
D017931:DNA Primers; D014280:Triglycerides; D000217:Acyltransferases; C494882:Dgat1 protein, mouse; C494883:Dgat1 protein, rat; D051048:Diacylglycerol O-Acyltransferase