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Journal of Lipid Research, Vol. 49, 2283-2301, November 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Thematic Review

Thematic Review Series: Glycerolipids. DGAT enzymes and triacylglycerol biosynthesis

Chi-Liang Eric Yen^*, Scot J. Stone, Suneil Koliwad^,**,, Charles Harris^,**, and Robert V. Farese, Jr.^1,,**,,

^* Department of Nutritional Sciences, University of Wisconsin, Madison, WI 53706
Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, San Francisco, CA 94141
^** Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94141
Department of Medicine, University of California, San Francisco, San Francisco, CA 94141
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94141

Published, JLR Papers in Press, August 29, 2008.

This work was supported by American Heart Association Scientist Development Grants (C-L.E.Y., S.J.S.), an A.P. Giannini Foundation Award (S.K.), National Institutes of Health Grant DK-56084 (R.V.F.), the Sandler Family Supporting Foundation, and the J. David Gladstone Institutes.

² TG biosynthesis can also occur through acyl-CoA-independent enzymes. For example, DG transacylase, an enzyme present in rodent small intestine, catalyses the direct transfer of a fatty acyl group from one DG to a second DG, yielding TG and MG products (173), and phospholipid:diacylglycerol transacylase catalyses the production of TG in a similar reaction, in which a fatty acyl group from the sn-2 position of phosphatidylcholine is transferred to DG. This latter pathway accounts for a substantial fraction of TG biosynthesis in yeast and plants (174). These acyl-CoA-independent mechanisms of TG synthesis will not be reviewed further here. We also will not review bacterial DGAT enzymes, which utilize acyl-CoA but are unrelated by sequence homology to mammalian DGAT1 and DGAT2 (175).

¹ To whom correspondence should be addressed. e-mail: bfarese{at}gladstone.ucsf.edu

Triacylglycerols (triglycerides) (TGs) are the major storage molecules of metabolic energy and FAs in most living organisms. Excessive accumulation of TGs, however, is associated with human diseases, such as obesity, diabetes mellitus, and steatohepatitis. The final and the only committed step in the biosynthesis of TGs is catalyzed by acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. The genes encoding two DGAT enzymes, DGAT1 and DGAT2, were identified in the past decade, and the use of molecular tools, including mice deficient in either enzyme, has shed light on their functions. Although DGAT enzymes are involved in TG synthesis, they have distinct protein sequences and differ in their biochemical, cellular, and physiological functions. Both enzymes may be useful as therapeutic targets for diseases. Here we review the current knowledge of DGAT enzymes, focusing on new advances since the cloning of their genes, including possible roles in human health and diseases.

Supplementary key words triacylglycerols • triglycerides • acyl-CoA:diacylglycerol acyltransferase • diacylglycerol • fatty acyl-CoA • lipoprotein • adipose • obesity • intestine • mammary gland

Abbreviations: ACAT, acyl-CoA:cholesterol acyltransferase; AMPK, AMP-activated kinase; apoB, apolipoprotein B; ARAT, acyl-CoA:retinol acyltransferase; ASO, anti-sense oligonucleotide; DG, diacylglycerol; DGAT, acyl-CoA:diacylglycerol acyltransferase; ER, endoplasmic reticulum; GPAT, glycerol-phosphate acyltranserase; MG, monoacylglycerol; MGAT, acyl-CoA:monoacylglycerol acyltransferase; SCD, stearoyl-CoA desaturase; SREBP, sterol-regulatory element binding protein; TG, triacylglycerol (triglyceride); WAT, white adipose tissue; XBP1, X-box binding protein 1

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