|Farese, Robert, Jr.|
Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/4/2002
Publication Date: 4/16/2002
Citation: Buhman, K.K., Smith, S.J., Stone, S.J., Repa, J.J., Wong, J.S., Knapp, F.F., Burri, B.J., Hamilton, R.L., Abumrad, N.A., Farese, R.V. 2002. DGAT1 IS NOT ESSENTIAL FOR INTESTINAL TRIACYLGLYCEROL ABSORPTION OR CHYLOMICRON SYNTHESIS. Journal of Biological Chemistry. Vol 277, No 28: 25474-25479, 2002. Interpretive Summary: The genetics that control vitamin A and fat metabolism are complex. We investigated an important component of vitamin A and fat metabolism, DGAT1, in mice. We expected that mice that did not have DGAT1 would have poor fat and vitamin A metabolism. Instead, they seemed normal. We found that two other components of vitamin A and fat metabolism appeared to take over the functions of DGAT1. Therefore, our results show that fat and vitamin A metabolism have multiple mechanisms, which is not surprising since they are important for health and growth.
Technical Abstract: Dieatry triacylglycerols are a major source of energy for animals. The absorption of dietary triacylglycerols involves their hydrolysis to free fatty acids and monoacylglycerols in the intestinal lumen, the uptake of these products into enterocytes, the resynthesis of triacylgylcerols, and the incorporation of newly synthesized triacylglycerols into nascent chylomicrons for secretion. Inenterocytes, the final step in triacylglycerol synthesis is believed to be catalyzed primarily through the actions of acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. In this study, we analyzed interstinal triacylglycerol aborption and chylomicron synthesis and secretion in DGAT1-deficient (Dgat1-/-) mice. Surprisingly, DGAT1 was not essential for quantitative dietary triacylglycerol absorption, even in mice fed a high fat diet, or for the synthesis of chylomicrons. However, Dgat1-/- mice had reduced portabsorptive chylomicronemia (1 h after a high fat challenge) and accumulated neutral-lipid droplets in the cytoplasm of enterocytes when chronically fed a high fat diet. These results suggest a reduced rate of triacylglycerol absorption in Dgat1-/- mice. Analysis of intestine from Dgat1-/- mice revealed activity for to other enzymes, DGAT2 and diacylglycerol transacylase, that catalyze triacylglycerol synthesis and apparently help to compensate for the absence of DGAT1. Our findings indicate thta multiple mechanisms for triacylglycerol synthesis in he intestine facilitate triacylglycerol absorption.