Hepatic knockdown of mitochondrial GPAT1 in ob/ob mice improves metabolic profile

Biochemical and Biophysical Research Communications

Volumn 349, Issue 1, 2006, Pages 439-448

  Xu, Haiyan ^a   Wilcox, Denise ^a   Nguyen, Phong ^a   Voorbach, Martin ^a   Suhar, Thomas ^a   Morgan, Sheryl J ^a   An, W Frank ^b   Ge, Lin ^b   Green, Jack ^b   Wu, Zhidan ^b   Gimeno, Ruth E ^b   Reilly, Regina ^a   Jacobson, Peer B ^a   Collins, Christine A ^a   Landschulz, Katherine ^a   Surowy, Terry ^a  

^a ABBOTT LABORATORIES   (United States)

^b MILLENNIUM PHARMACEUTICALS INC   (United States)

Author keywords

Adenovirus; mtGPAT1; ob ob mice; Obesity; RNA interference

Indexed keywords

ADENOVIRUS VECTOR; CHOLESTEROL; DIACYLGLYCEROL; FATTY ACID; GLUCOSE; GLYCEROL 3 PHOSPHATE ACYLTRANSFERASE; GLYCEROL 3 PHOSPHATE ACYLTRANSFERASE 1; MESSENGER RNA; TRIACYLGLYCEROL; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CHOLESTEROL BLOOD LEVEL; ENZYME ACTIVITY; ENZYME LOCALIZATION; GLUCOSE BLOOD LEVEL; HUMAN; HUMAN CELL; KNOCKOUT MOUSE; LIPID COMPOSITION; LIPID METABOLISM; LIPOGENESIS; LIVER MICROSOME; LIVER MITOCHONDRION; MALE; METABOLIC INHIBITION; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; OBESITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; RNA INTERFERENCE;

ADENOVIRIDAE; ANIMALS; BASE SEQUENCE; GLYCEROL-3-PHOSPHATE O-ACYLTRANSFERASE; HEPATOCYTES; HUMANS; LIVER; MALE; MICE; MICE, KNOCKOUT; MICE, OBESE; MITOCHONDRIA; MOLECULAR SEQUENCE DATA; OBESITY; TRIGLYCERIDES;

ADENOVIRIDAE; RODENTIA;

EID: 33748323244     PISSN: 0006291X     EISSN: 10902104     Source Type: Journal    
DOI: 10.1016/j.bbrc.2006.08.071     Document Type: Article

References (31)

1. Zimmet P., Alberti K.G., and Shaw J. Global and societal implications of the diabetes epidemic. Nature 414 (2001) 782-787
2. Kopelman P.G. Obesity as a medical problem. Nature 404 (2000) 635-643
3. Sul H.S., and Wang D. Nutritional and hormonal regulation of enzymes in fat synthesis: studies of fatty acid synthase and mitochondrial glycerol-3-phosphate acyltransferase gene transcription. Annu. Rev. Nutr. 18 (1998) 331-351
4. Shi Y., and Burn P. Lipid metabolic enzymes: emerging drug targets for the treatment of obesity. Nat. Rev. Drug Discov. 3 (2004) 695-710
5. Daae L.N., and Bremer J. The acylation of glycerophosphate in rat liver. A new assay procedure for glycerophosphate acylation, studies on its subcellular and submitochondrial localization and determination of the reaction products. Biochim. Biophys. Acta 210 (1970) 92-104
6. Lewin T.M., Schwerbrock N.M., Lee D.P., and Coleman R.A. Identification of a new glycerol-3-phosphate acyltransferase isoenzyme, mtGPAT2, in mitochondria. J. Biol. Chem. 279 (2004) 13488-13495
7. Shin D.H., Paulauskis J.D., Moustaid N., and Sul H.S. Transcriptional regulation of p90 with sequence homology to Escherichia coli glycerol-3-phosphate acyltransferase. J. Biol. Chem. 266 (1991) 23834-23839
8. Lewin T.M., Granger D.A., Kim J.H., and Coleman R.A. Regulation of mitochondrial sn-glycerol-3-phosphate acyltransferase activity: response to feeding status is unique in various rat tissues and is discordant with protein expression. Arch. Biochem. Biophys. 396 (2001) 119-127
9. Dircks L.K., and Sul H.S. Mammalian mitochondrial glycerol-3-phosphate acyltransferase. Biochim. Biophys. Acta 1348 (1997) 17-26
10. Coleman R.A., and Lee D.P. Enzymes of triacylglycerol synthesis and their regulation. Prog. Lipid Res. 43 (2004) 134-176
11. Linden D., William-Olsson L., Rhedin M., Asztely A.K., Clapham J.C., and Schreyer S. Overexpression of mitochondrial GPAT in rat hepatocytes leads to decreased fatty acid oxidation and increased glycerolipid biosynthesis. J. Lipid Res. 45 (2004) 1279-1288
12. Jamdar S.C., and Cao W.F. Triacylglycerol biosynthetic enzymes in lean and obese Zucker rats. Biochim. Biophys. Acta 1255 (1995) 237-243
13. Lee Y., Hirose H., Zhou Y.T., Esser V., McGarry J.D., and Unger R.H. Increased lipogenic capacity of the islets of obese rats: a role in the pathogenesis of NIDDM. Diabetes 46 (1997) 408-413
14. Lewin T.M., Wang S., Nagle C.A., Van Horn C.G., and Coleman R.A. Mitochondrial glycerol-3-phosphate acyltransferase-1 directs the metabolic fate of exogenous fatty acids in hepatocytes. Am. J. Physiol. Endocrinol. Metab. 288 (2005) E835-E844
15. Igal R.A., Wang S., Gonzalez-Baro M., and Coleman R.A. Mitochondrial glycerol phosphate acyltransferase directs the incorporation of exogenous fatty acids into triacylglycerol. J. Biol. Chem. 276 (2001) 42205-42212
16. Gonzalez-Baro M.R., Granger D.A., and Coleman R.A. Mitochondrial glycerol phosphate acyltransferase contains two transmembrane domains with the active site in the N-terminal domain facing the cytosol. J. Biol. Chem. 276 (2001) 43182-43188
17. Park H., Kaushik V.K., Constant S., Prentki M., Przybytkowski E., Ruderman N.B., and Saha A.K. Coordinate regulation of malonyl-CoA decarboxylase, sn-glycerol-3-phosphate acyltransferase, and acetyl-CoA carboxylase by AMP-activated protein kinase in rat tissues in response to exercise. J. Biol. Chem. 277 (2002) 32571-32577
18. Muoio D.M., Seefeld K., Witters L.A., and Coleman R.A. AMP-activated kinase reciprocally regulates triacylglycerol synthesis and fatty acid oxidation in liver and muscle: evidence that sn-glycerol-3-phosphate acyltransferase is a novel target. Biochem. J. 338 Pt. 3 (1999) 783-791
19. Linden D., William-Olsson L., Ahnmark A., Ekroos K., Hallberg C., Sjogren P., Becker B., Svensson L., Clapham J.C., Oscarsson J., and Schreyer S. Liver-directed overexpression of mitochondrial glycerol-3-phosphate acyltransferase results in hepatic steatosis, increased triacylglycerol secretion and reduced fatty acid oxidation. FASEB J. 20 (2006) 434-443
20. Hammond L.E., Gallagher P.A., Wang S., Hiller S., Kluckman K.D., Posey-Marcos E.L., Maeda N., and Coleman R.A. Mitochondrial glycerol-3-phosphate acyltransferase-deficient mice have reduced weight and liver triacylglycerol content and altered glycerolipid fatty acid composition. Mol. Cell Biol. 22 (2002) 8204-8214
21. Hammond L.E., Neschen S., Romanelli A.J., Cline G.W., Ilkayeva O.R., Shulman G.I., Muoio D.M., and Coleman R.A. Mitochondrial glycerol-3-phosphate acyltransferase-1 is essential in liver for the metabolism of excess acyl-CoAs. J. Biol. Chem. 280 (2005) 25629-25636
22. Neschen S., Morino K., Hammond L.E., Zhang D., Liu Z.X., Romanelli A.J., Cline G.W., Pongratz R.L., Zhang X.M., Choi C.S., Coleman R.A., and Shulman G.I. Prevention of hepatic steatosis and hepatic insulin resistance in mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 knockout mice. Cell Metab. 2 (2005) 55-65
23. Koo S.H., Flechner L., Qi L., Zhang X., Screaton R.A., Jeffries S., Hedrick S., Xu W., Boussouar F., Brindle P., Takemori H., and Montminy M. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature 437 (2005) 1109-1111
24. Taniguchi C.M., Ueki K., and Kahn R. Complementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism. J. Clin. Invest. 115 (2005) 718-727
25. Bahl J.J., Matsuda M., DeFronzo R.A., and Bressler R. In vitro and in vivo suppression of gluconeogenesis by inhibition of pyruvate carboxylase. Biochem. Pharmacol. 53 (1997) 67-74
26. Williamson J.R., Kreisberg R.A., and Felts P.W. Mechanism for the stimulation of gluconeogenesis by fatty acids in perfused rat liver. Proc. Natl. Acad. Sci. USA 56 (1966) 247-254
27. Massillon D., Barzilai N., Hawkins M., Prus-Wertheimer D., and Rossetti L. Induction of hepatic glucose-6-phosphatase gene expression by lipid infusion. Diabetes 46 (1997) 153-157
28. Boden G., She P., Mozzoli M., Cheung P., Gumireddy K., Reddy P., Xiang X., Luo Z., and Ruderman N. Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-kappaB pathway in rat liver. Diabetes 54 (2005) 3458-3465
29. Boden G., and Carnell L.H. Nutritional effects of fat on carbohydrate metabolism. Best Pract. Res. Clin. Endocrinol. Metab. 17 (2003) 399-410
30. Vancura A., and Haldar D. Purification and characterization of glycerophosphate acyltransferase from rat liver mitochondria. J. Biol. Chem. 269 (1994) 27209-27215
31. Yet S.F., Moon Y.K., and Sul H.S. Purification and reconstitution of murine mitochondrial glycerol-3-phosphate acyltransferase. Functional expression in baculovirus-infected insect cells. Biochemistry 34 (1995) 7303-7310