Submitted on November 30, 2006
Accepted on December 5, 2006
Function of mitochondrial GPAT1 in the regulation of triacylglycerol biosynthesis and insulin action
Maria R. Gonzalez-Baró1, Tal M. Lewin2, and Rosalind A. Coleman3*
1 Biochemistry, Instituto de Investigaciones Bioquímicas de La Plata, La Plata, Argentina
2 Nutrition, University of North Carolina at Chapel Hill,, Chapel Hill, North Carolina, United States
3 Chapel Hill, United States; Nutrition, University of North Carolina at Chapel Hill,, Chapel Hill, North Carolina, United States
* To whom correspondence should be addressed. E-mail: rcoleman{at}unc.edu.
GPAT1, one of four known glycerol-3-phosphate acyltransferase isoforms, is located on the mitochondrial outer membrane, allowing reciprocal regulation with carnitine palmitoyltransferase-1. GPAT1 is upregulated transcriptionally by insulin and SREBP-1c and down-regulated acutely by AMP-activated protein kinase, consistent with a role in triacylglycerol synthesis. Knockout and overexpression studies suggest that GPAT1 is critical for the development of hepatic steatosis, and that steatosis initiated by overexpression of GPAT1 causes hepatic, and perhaps also peripheral, insulin resistance. Future questions include the function of GPAT1 in relation to the other GPAT isoforms and whether the lipid intermediates synthesized by GPAT and downstream enzymes in the pathway of glycerolipid biosynthesis participate in intracellular signaling pathways.
