Published online before print November 29, 2004, doi: 10.1161/01.ATV.0000151874.81059.ad
© 2005 American Heart Association, Inc.
Brief Reviews |
Inhibition of Triglyceride Synthesis as a Treatment Strategy for Obesity
Lessons From DGAT1-Deficient Mice
From the Department of Medical Sciences (H.C.C.), Amgen Inc, Thousand Oaks; the Gladstone Institute of Cardiovascular Disease (R.V.F.) and the Department of Medicine (R.V.F.), University of California, San Francisco.
Correspondence to Dr Robert V. Farese, Jr, Gladstone Institute of Cardiovascular Disease, 1650 Owens St, San Francisco, CA 94158. E-mail bfarese{at}gladstone.ucsf.edu
Series Editor: Daniel J. Rader
Novel Approaches to the Treatment of Dyslipidemia
ATVB In Focus
Because the ability to make triglycerides is essential for the accumulation of adipose tissue, inhibition of triglyceride synthesis may ameliorate obesity and its related medical consequences. Acyl coenzyme A (CoA):diacylglycerol acyltransferase 1 (DGAT1) is 1 of 2 DGAT enzymes that catalyze the final reaction in the known pathways of mammalian triglyceride synthesis. Mice lacking DGAT1 are resistant to obesity and have increased sensitivity to insulin and leptin. DGAT1-deficient mice are also resistant to diet-induced hepatic steatosis. The effects of DGAT1 deficiency on energy and glucose metabolism result in part from the altered secretion of adipocyte-derived factors. Although complete DGAT1 deficiency causes alopecia and impairs development of the mammary gland, these abnormalities are not observed in mice with partial DGAT1 deficiency. These findings suggest that pharmacological inhibition of DGAT1 may be a feasible therapeutic strategy for human obesity and type 2 diabetes.
Acyl CoA:diacylglycerol acyltransferase 1 (DGAT1) is a key enzyme in the mammalian triglyceride synthesis pathway. Because mice lacking DGAT1 are resistant to obesity and have increased sensitivity to insulin, pharmacologic inhibition of DGAT1 may represent a feasible therapeutic strategy for human obesity and type 2 diabetes.
Key Words: acyl CoA:diacylglycerol acyltransferase • energy • glucose • metabolism • insulin resistance • type 2 diabetes
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Arterioscler. Thromb. Vasc. Biol. 2005 25: 480-481.
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