Knockdown of Acyl-CoA:diacylglycerol acyltransferase 2 with antisense oligonucleotide reduces VLDL TG and ApoB secretion in mice

Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

Volumn 1781, Issue 3, 2008, Pages 97-104

  Liu, Ying ^a   Millar, John S ^a   Cromley, Debra A ^a   Graham, Mark ^b   Crooke, Rosanne ^b   Billheimer, Jeffrey T ^a   Rader, Daniel J ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b ISIS PHARMACEUTICALS   (United States)

Author keywords

Acyl CoA:diacylglycerol acyltransferase; Antisense oligonucleotide; Apolipoprotein B; Obesity; Triacylglycerol synthesis; VLDL secretion

Indexed keywords

ANTISENSE OLIGODEOXYNUCLEOTIDE; APOLIPOPROTEIN B; CHOLESTEROL; DIACYLGLYCEROL ACYLTRANSFERASE; DIACYLGLYCEROL ACYLTRANSFERASE 1; DIACYLGLYCEROL ACYLTRANSFERASE 2; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; VERY LOW DENSITY LIPOPROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTISENSE THERAPY; ARTICLE; BODY FAT DISTRIBUTION; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DOSE RESPONSE; DRUG DOSE INCREASE; ENZYME ACTIVITY; ENZYME BLOOD LEVEL; ENZYME INACTIVATION; FATTY LIVER; FEMALE; GENE EXPRESSION; HYPERTRIGLYCERIDEMIA; LIPOGENESIS; LIPOPROTEIN BLOOD LEVEL; LIPOPROTEIN SECRETION; MOUSE; NONHUMAN; OBESITY; PRIORITY JOURNAL; THERAPY EFFECT; TREATMENT OUTCOME; TREATMENT RESPONSE; TRIACYLGLYCEROL BLOOD LEVEL; WEIGHT GAIN; WILD TYPE;

MUS;

EID: 39849093869     PISSN: 13881981     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbalip.2008.01.001     Document Type: Article

References (34)

1. M.A. Austin Triglyceride, small, dense low-density lipoprotein, and the atherogenic lipoprotein phenotype Curr. Atheroscler. Rep. 2 2000 200 207
2. P. Cullen Evidence that triglycerides are an independent coronary heart disease risk factor Am. J. Cardiol. 86 2000 943 949
3. H.N. Ginsberg New perspectives on atherogenesis: role of abnormal triglyceride-rich lipoprotein metabolism Circulation 106 2002 2137 2142
4. G.F. Gibbons D. Wiggins A.M. Brown A.M. Hebbachi Synthesis and function of hepatic very-low-density lipoprotein Biochem. Soc. Trans. 32 2004 59 64
5. G.F. Gibbons S.M. Bartlett C.E. Sparks J.D. Sparks Extracellular fatty acids are not utilized directly for the synthesis of very-low-density lipoprotein in primary cultures of rat hepatocytes Biochem. J. 287 Pt 3 1992 749 753
6. E.A. Fisher H.N. Ginsberg Complexity in the secretory pathway: the assembly and secretion of Apolipoprotein B-containing lipoproteins J. Biol. Chem. 277 2002 17377 17380
7. J.J. Liang P. Oelkers C. Guo P.-C. Chu J.L. Dixon H.N. Ginsberg S.L. Sturley Overexpression of human diacylglycerol acyltransferase 1, Acyl-CoA:cholesterol acyltransferase 1, or Acyl-CoA:cholesterol acyltransferase 2 stimulates secretion of Apolipoprotein B-containing lipoproteins in McA-RH7777 cells J. Biol. Chem. 279 2004 44938 44944
8. T.L. Visscher J.C. Seidell The public health impact of obesity Annu. Rev. Public Health 22 2001 355 375
9. L.A. Adams P. Angulo Recent concepts in non-alcoholic fatty liver disease Diabet. Med. 22 2005 1129 1133
10. R.M. Bell R.A. Coleman Enzymes of glycerolipid synthesis in eukaryotes Annu. Rev. Biochem. 49 1980 459 487
11. S. Cases S.J. Smith Y.W. Zheng H.M. Myers S.R. Lear E. Sande S. Novak C. Collins C.B. Welch A.J. Lusis S.K. Erickson R.V. Farese Jr. Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis Proc. Natl. Acad. Sci. U. S. A. 95 1998 13018 13023
12. S. Cases S.J. Stone P. Zhou E. Yen B. Tow K.D. Lardizabal T. Voelker R.V. Farese Jr. Cloning of DGAT2, a second mammalian diacylglycerol acyltransferase, and related family members J. Biol. Chem. 276 2001 38870 38876
13. P. Oelkers A. Behari D. Cromley J.T. Billheimer S.L. Sturley Characterization of two human genes encoding acyl coenzyme A:cholesterol acyltransferase-related enzymes J. Biol. Chem. 273 1998 26765 26771
14. J. Cao P. Burn Y. Shi Properties of the mouse intestinal Acyl-CoA:monoacylglycerol acyltransferase, MGAT2 J. Biol. Chem. 278 2003 25657 25663
15. C.-L.E. Yen S.J. Stone S. Cases P. Zhou R.V. Farese Jr. Identification of a gene encoding MGAT1, a monoacylglycerol acyltransferase PNAS 99 2002 8512 8517
16. J.B. Cheng D.W. Russell Mammalian wax biosynthesis: II. Expression cloning of wax synthase cDNAs encoding a member of the acyltransferase enzyme family J. Biol. Chem. 279 2004 37798 37807
17. A.R. Turkish A.L. Henneberry D. Cromley M. Padamsee P. Oelkers H. Bazzi A.M. Christiano J.T. Billheimer S.L. Sturley Identification of two novel human acyl-CoA wax alcohol acyltransferases: members of the diacylglycerol acyltransferase 2 (DGAT2) gene superfamily J. Biol. Chem. 280 2005 14755 14764
18. S.J. Smith S. Cases D.R. Jensen H.C. Chen E. Sande B. Tow D.A. Sanan J. Raber R.H. Eckel R.V. Farese Jr. Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat Nat. Genet. 25 2000 87 90
19. S.J. Stone H.M. Myers S.M. Watkins B.E. Brown K.R. Feingold P.M. Elias R.V. Farese Jr. Lipopenia and skin barrier abnormalities in DGAT2-deficient mice J. Biol. Chem. 279 2004 11767 11776
20. T. Yamazaki E. Sasaki C. Kakinuma T. Yano S. Miura O. Ezaki Increased very low density lipoprotein secretion and gonadal fat mass in mice overexpressing liver DGAT1 J. Biol. Chem. 280 2005 21506 21514
21. J.S. Millar S.J. Stone U.J. Tietge B. Tow J.T. Billheimer J.S. Wong R.L. Hamilton R.V. Farese Jr. D.J. Rader Short-term hepatic overexpression of DGAT1 or DGAT2 in female mice increases hepatic triglyceride synthesis without changing VLDL triglyceride or ApoB production J. Lipid Res. 47 10 2006 2297 2305
22. R.S. Geary T.A. Watanabe L. Truong S. Freier E.A. Lesnik N.B. Sioufi H. Sasmor M. Manoharan A.A. Levin Pharmacokinetic properties of 2′- O -(2-methoxyethyl)-modified oligonucleotide analogs in rats J. Pharmacol. Exp. Ther. 296 2001 890 897
23. R.Z. Yu R.S. Geary D.K. Monteith J. Matson L. Truong J. Fitchett A.A. Levin Tissue disposition of 2′- O -(2-methoxy) ethyl modified antisense oligonucleotides in monkeys J. Pharm. Sci. 93 2004 48 59
24. R.Z. Yu R.S. Geary J.M. Leeds T. Watanabe M. Moore J. Fitchett J. Matson T. Burckin M.V. Templin A.A. Levin Comparison of pharmacokinetics and tissue disposition of an antisense phosphorothioate oligonucleotide targeting human Ha-ras mRNA in mouse and monkey J. Pharm. Sci. 90 2001 182 193
25. X.X. Yu S.F. Murray S.K. Pandey S.L. Booten D. Bao X.Z. Song S. Kelly S. Chen R. McKay B.P. Monia S. Bhanot Antisense oligonucleotide reduction of DGAT2 expression improves hepatic steatosis and hyperlipidemia in obese mice Hepatology 42 2005 362 371
26. J.S. Millar D.A. Cromley M.G. McCoy D.J. Rader J.T. Billheimer Determining hepatic triglyceride production in mice: comparison of poloxamer 407 with Triton WR-1339 J. Lipid Res. 46 2005 2023 2028
27. J.S. Millar C. Maugeais I.V. Fuki D.J. Rader Normal production rate of apolipoprotein B in LDL receptor-deficient mice Arterioscler. Thromb. Vasc. Biol. 22 2002 989 994
28. B. Miao S. Zondlo S. Gibbs D. Cromley V.P. Hosagrahara T.G. Kirchgessner J. Billheimer R. Mukherjee Raising HDL cholesterol without inducing hepatic steatosis and hypertriglyceridemia by a selective LXR modulator J. Lipid Res. 45 2004 1410 1417
29. M.D. Orland K. Anwar D. Cromley C.H. Chu L. Chen J.T. Billheimer M.M. Hussain D. Cheng Acyl coenzyme A dependent retinol esterification by acyl coenzyme A:diacylglycerol acyltransferase 1 Biochim. Biophys. Acta 1737 2005 76 82
30. R. Suzuki K. Tobe M. Aoyama K. Sakamoto M. Ohsugi N. Kamei S. Nemoto A. Inoue Y. Ito S. Uchida K. Hara T. Yamauchi N. Kubota Y. Terauchi T. Kadowaki Expression of DGAT2 in white adipose tissue is regulated by central leptin action J. Biol. Chem. 280 2005 3331 3337
31. W.C. Man M. Miyazaki K. Chu J. Ntambi Colocalization of SCD1 and DGAT2: implying preference for endogenous monounsaturated fatty acids in triglyceride synthesis J. Lipid Res. 47 2006 1928 1939
32. C.L. Yen M. Monetti B.J. Burri R.V. Farese Jr. The triacylglycerol synthesis enzyme DGAT1 also catalyzes the synthesis of diacylglycerols, waxes, and retinyl esters J. Lipid Res. 46 2005 1502 1511
33. L.L. Rudel R.G. Lee T.L. Cockman Acyl coenzyme A: cholesterol acyltransferase types 1 and 2: structure and function in atherosclerosis Curr. Opin. Lipidol. 12 2001 121 127
34. J. Millar J. Billheimer Diacylglycerol: acylcoA acyltransferases (DGATs) as therapeutic targets for cardiovascular disease C. Packard D. Rader Lipids and Atherosclerosis 2006 Taylor and Fraser Group