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Molecular and Cellular Biology, December 2002, p. 8204-8214, Vol. 22, No. 23
0270-7306/02/$04.00+0 DOI: 10.1128/MCB.22.23.8204-8214.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Mitochondrial Glycerol-3-Phosphate Acyltransferase-Deficient Mice Have Reduced Weight and Liver Triacylglycerol Content and Altered Glycerolipid Fatty Acid Composition
Linda E. Hammond,1 Patricia A. Gallagher,1 Shuli Wang,1 Sylvia Hiller,2 Kimberly D. Kluckman,2 Eugenia L. Posey-Marcos,1,
Nobuyo Maeda,1,2 and Rosalind A. Coleman1*
Department of Nutrition,1
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina 275992
Received 1 July 2002/
Returned for modification 12 August 2002/
Accepted 10 September 2002
Microsomal and mitochondrial isoforms of glycerol-3-phosphate acyltransferase (GPAT; E.C. 2.3.1.15) catalyze the committed step in glycerolipid synthesis. The mitochondrial isoform, mtGPAT, was believed to control the positioning of saturated fatty acids at the sn-1 position of phospholipids, and nutritional, hormonal, and overexpression studies suggested that mtGPAT activity is important for the synthesis of triacylglycerol. To determine whether these purported functions were true, we constructed mice deficient in mtGPAT. mtGPAT-/- mice weighed less than controls and had reduced gonadal fat pad weights and lower hepatic triacylglycerol content, plasma triacylglycerol, and very low density lipoprotein triacylglycerol secretion. As predicted, in mtGPAT-/- liver, the palmitate content was lower in triacylglycerol, phosphatidylcholine, and phosphatidylethanolamine. Positional analysis revealed that mtGPAT-/- liver phosphatidylethanolamine and phosphatidylcholine had about 21% less palmitate in the sn-1 position and 36 and 40%, respectively, more arachidonate in the sn-2 position. These data confirm the important role of mtGPAT in the synthesis of triacylglycerol, in the fatty acid content of triacylglycerol and cholesterol esters, and in the positioning of specific fatty acids, particularly palmitate and arachidonate, in phospholipids. The increase in arachidonate may be functionally significant in terms of eicosanoid production.
* Corresponding author. Mailing address: 2209 McGavran-Greenberg Bldg., Pittsboro St., University of North Carolina, Chapel Hill, NC 27599. Phone: (919) 966-7213. Fax: (919) 966-7216. E-mail: rcoleman{at}unc.edu.
Present address: NCBI User Services, NCBI/NLM/NIH, Bethesda, MD 20894.
Molecular and Cellular Biology, December 2002, p. 8204-8214, Vol. 22, No. 23
0022-538X/02/$04.00+0 DOI: 10.1128/MCB.22.23.8204-8214.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
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Copyright © 2002 by the American Society for Microbiology. All rights reserved.