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ARS Home » Pacific West Area » Davis, California » Western Human Nutrition Research Center » Research » Publications at this Location » Publication #169214
Title: THE TRIACYLGLYCEROL SYNTHESIS ENZYME DGAT1 ALSO CATALYZES THE SYNTHESIS OF DIACYLGLYCEROLS, WAXES, AND RETINYL ESTERS

Author
item YEN, CHI-LIANG - GLADSTONE INST.CARDIO.DIS
item MONETTI, MARA - GALDSTONE INST.CARDIO D.
item Burri, Betty
item FARESE, JR - UCSF, GALDSTONE, CARDIO

Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/4/2005
Publication Date: 4/16/2005
Citation: Yen, C.E., Monetti, M., Burri, B.J., Farese, J. The triacylglycerol synthesis enzyme dgat1 also catalyzes the synthesis of diacylglycerols, waxes, and retinyl esters. Journal of Lipid Research.Vol.46:1502-1511, 2005.

Interpretive Summary: Vitamin A is essential for human health: it is necessary for normal growth and development. Vitamin A deficiency is a leading cause of blindness, and of infant and maternal mortality in Asia, Africa, and South and Central America. Vitamin A deficiency would be much more common than it is now, except for the fact that vitamin A is stored in our livers, where it can be released during periods of malnutrition. Vitamin A from food has to be chemically transformed before it can be stored safely in our livers. The details of this transformation, including the molecules and mechanisms involved, are largely unknown. We discovered that a molecule that is responsible for the last step of triglyceride formation is also involved in the transformation of vitamin A to its storage form. Only a few of the molecules involved in this process have been identified, so identifying this molecule is important. Understanding the mechanisms involved in vitamin A storage might eventually lead to improved methods for identifying people at risk for vitamin A deficiency, and improved treatments of vitamin A deficiency.

Technical Abstract: The final step in the biosynthesis of triacylglycerol is catlyzed by acyl CoA:diacylglycerol acyltransferase (DGAT) enzymes. The two known DGATs, DGAT1 and DGAT2, are encoded by unrelated genes. Although knockout mice dificient in DGAT1 and DGAT2 both have reduced triacylglycerol content, these mice have disparate phenotypes. DGAT1-deficient mice have modest reductions in tissue triacylglycerols, are resistant to diet-induced obestiy, and have developmental abnormalities in the skin and mammary glands. DGAT2-deficient mice have severely reduced triacylglycerol content and die hours after birth. These observations prompted us to investigate whether the two enzymes have unrecognized functional differences. We now report that DGAT1 performs additional acyltransferase activities, including that of an acyl CoA:retinol acyltransferase (ARAT), which catalyzes the synthesis of retinol esters from retinol and fatty acyl CoA. Membranes from insect cells expressing DGAT1, but not those expressing DGAT2, catalyzed the synthesis of retinol esters in in vitro assays with labeled palmitoyl CoA or retinol substrates. Retinol ester accumulation was higher in intact mamalian cells overexpressing DGAT1 and lower in DAGT1-deificient mouse embryonic fibroblasts than in control cells. Liver, kidney, and testis homogenates from DGAT1-deficient mice exhibited reduced ARAT activities, and when DGAT1-deficient mice were fed diets high in retinol, their livers accumulated more unesterified retinol than did those of wild-type mice. Our findings indicate that DGAT1 functions as an ARAT in vitro and may play a role in retinol metabolism in vivo.