Activation of PPARα and PPARγ reduces triacylglycerol synthesis in rat hepatoma cells by reduction of nuclear SREBP-1

European Journal of Pharmacology

Volumn 605, Issue 1-3, 2009, Pages 23-30

  König, Bettina ^a   Koch, Alexander ^a   Spielmann, Julia ^a   Hilgenfeld, Christian ^a   Hirche, Frank ^a   Stangl, Gabriele I ^a   Eder, Klaus ^a  

^a MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

Author keywords

Fao cells; Insig; PPAR ; PPAR ; SREBP 1c; Triacylglycerol synthesis

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; FATTY ACID; FATTY ACID SYNTHASE; FIBRIC ACID DERIVATIVE; GLYCEROL 3 PHOSPHATE ACYLTRANSFERASE; MESSENGER RNA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PIRINIXIC ACID; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C; TRIACYLGLYCEROL; TROGLITAZONE; CHROMAN DERIVATIVE; INSIG1 PROTEIN, HUMAN; INSIG2 PROTEIN, HUMAN; MEMBRANE PROTEIN; PYRIMIDINE DERIVATIVE; SIGNAL PEPTIDE; STEROL REGULATORY ELEMENT BINDING PROTEIN 1;

ANIMAL CELL; ARTICLE; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DRUG MECHANISM; FATTY ACID SYNTHESIS; GENE; GENE EXPRESSION REGULATION; INSULIN INDUCED GENE 1; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN FUNCTION; RAT; ANIMAL; BIOSYNTHESIS; DRUG POTENTIATION; GENETICS; LIVER CELL CARCINOMA; LIVER TUMOR; METABOLISM; TUMOR CELL LINE; UPREGULATION;

ANIMALS; CARCINOMA, HEPATOCELLULAR; CELL LINE, TUMOR; CHROMANS; FATTY ACID SYNTHETASE COMPLEX; GLYCEROL-3-PHOSPHATE O-ACYLTRANSFERASE; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; LIVER NEOPLASMS; MEMBRANE PROTEINS; PPAR ALPHA; PPAR GAMMA; PYRIMIDINES; RATS; RNA, MESSENGER; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; THIAZOLIDINEDIONES; TRIGLYCERIDES; UP-REGULATION;

EID: 60349084474     PISSN: 00142999     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejphar.2009.01.009     Document Type: Article

References (45)

1. Adams C.M., Reitz J., De Brabander J.K., Feramisco J.D., Li L., Brown M.S., and Goldstein J.L. Cholesterol and 25-hydroxycholesterol inhibit activation of SREBPs by different mechanisms, both involving SCAP and Insigs. J. Biol. Chem. 279 (2004) 52772-52780
2. Amemiya-Kudo M., Shimano H., Hasty A.H., Yahagi N., Yoshikawa T., Matsuzaka T., Okazaki H., Tamura Y., Iizuka Y., Ohashi K., Osuga J., Harada K., Gotoda T., Sato R., Kimura S., Ishibashi S., and Yamada N. Transcriptional activities of nuclear SREBP-1a, -1c, and -2 to different target promoters of lipogenic and cholesterogenic genes. J. Lipid Res. 43 (2002) 1220-1235
3. Brown M.S., and Goldstein J.L. A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. Proc. Nat. Acad. Sci. U.S.A. 96 (1999) 11041-11048
4. Chinetti G., Fruchart J.C., and Staels B. Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm. Res. 49 (2000) 497-505
5. Davies G.F., McFie P.J., Khandelwal R.L., and Roesler W.J. Unique ability of troglitazone to up-regulate peroxisome proliferator-activated receptor-gamma expression in hepatocytes. J. Pharmacol. Exp. Ther. 300 (2002) 72-77
6. Desvergne B., and Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocrine Rev. 20 (1999) 649-688
7. Duval C., Chinetti G., Trottein F., Fruchart J.C., and Staels B. The role of PPARs in atherosclerosis. Trends Mol. Med. 8 (2002) 422-430
8. Eder K., Suelzle A., Skufca P., Brandsch C., and Hirche F. Effects of dietary thermoxidized fats on expression and activities of hepatic lipogenic enzymes in rats. Lipids 38 (2003) 31-38
9. Engelking L.J., Kuriyama H., Hammer R.E., Horton J.D., Brown M.S., Goldstein J.L., and Liang G. Overexpression of Insig-1 in the livers of transgenic mice inhibits SREBP processing and reduces insulin-stimulated lipogenesis. J. Clin. Invest. 113 (2004) 1168-1175
10. Fajas L., Auboeuf D., Raspe E., Schoonjans K., Lefebvre A.M., Saladin R., Najib J., Laville M., Fruchart J.C., Deeb S., Vidal-Puig A., Flier J., Briggs M.R., Staels B., Vidal H., and Auwerx J. The organization, promoter analysis, and expression of the human PPARgamma gene. J. Biol. Chem. 272 (1997) 18779-18789
11. Festuccia W.T., Laplante M., Berthiaume M., Gelinas Y., and Deshaies Y. PPARgamma agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control. Diabetologia 49 (2006) 2427-2436
12. Frick M.H., Elo O., Haapa K., Heinonen O.P., Heinsalmi P., Helo P., Huttunen J.K., Kaitaniemi P., Koskinen P., Manninen V., et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N. Engl. J. Med. 317 (1987) 1237-1245
13. Horton J.D., Goldstein J.L., and Brown M.S. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J. Clin. Invest. 109 (2002) 1125-1131
14. Hsu M.H., Savas U., Griffin K.J., and Johnson E.F. Regulation of human cytochrome P450 4F2 expression by sterol regulatory element-binding protein and lovastatin. J. Biol. Chem. 282 (2007) 5225-5236
15. Kakuma T., Lee Y., Higa M., Wang Z., Pan W., Shimomura I., and Unger R.H. Leptin, troglitazone, and the expression of sterol regulatory element binding proteins in liver and pancreatic islets. Proc. Natl. Acad. Sci. U S A 97 (2000) 8536-8541
16. Kast-Woelbern H.R., Dana S.L., Cesario R.M., Sun L., de Grandpre L.Y., Brooks M.E., Osburn D.L., Reifel-Miller A., Klausing K., and Leibowitz M.D. Rosiglitazone induction of Insig-1 in white adipose tissue reveals a novel interplay of peroxisome proliferator-activated receptor gamma and sterol regulatory element-binding protein in the regulation of adipogenesis. J. Biol. Chem. 279 (2004) 23908-23915
17. Klopotek A., Hirche F., and Eder K. PPAR gamma ligand troglitazone lowers cholesterol synthesis in HepG2 and Caco-2 cells via a reduced concentration of nuclear SREBP-2. Exp. Biol. Med. (Maywood) 231 (2006) 1365-1372
18. Knight B.L., Hebbachi A., Hauton D., Brown A.M., Wiggins D., Patel D.D., and Gibbons G.F. A role for PPARalpha in the control of SREBP activity and lipid synthesis in the liver. Biochem. J. 389 (2005) 413-421
19. König B., and Eder K. Differential action of 13-HPODE on PPARalpha downstream genes in rat Fao and human HepG2 hepatoma cell lines. J. Nutr. Biochem. 17 (2006) 410-418
20. König B., Koch A., Spielmann J., Hilgenfeld C., Stangl G.I., and Eder K. Activation of PPARalpha lowers synthesis and concentration of cholesterol by reduction of nuclear SREBP-2. Biochem. Pharmacol. 73 (2007) 574-585
21. Laplante M., Festuccia W.T., Soucy G., Gelinas Y., Lalonde J., and Deshaies Y. Involvement of adipose tissues in the early hypolipidemic action of PPARgamma agonism in the rat. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292 (2007) R1408-R1417
22. Lee G.Y., Kim N.H., Zhao Z.S., Cha B.S., and Kim Y.S. Peroxisomal-proliferator-activated receptor alpha activates transcription of the rat hepatic malonyl-CoA decarboxylase gene: a key regulation of malonyl-CoA level. Biochem. J. 378 (2004) 983-990
23. Lee P.C., Sever N., and Debose-Boyd R.A. Isolation of sterol-resistant Chinese hamster ovary cells with genetic deficiencies in both Insig-1 and Insig-2. J. Biol. Chem. 280 (2005) 25242-25249
24. Li Y., Nara T.Y., and Nakamura M.T. Peroxisome proliferator-activated receptor alpha is required for feedback regulation of highly unsaturated fatty acid synthesis. J. Lipid Res. 46 (2005) 2432-2440
25. Li X., Hansen P.A., Xi L., Chandraratna R.A., and Burant C.F. Distinct mechanisms of glucose lowering by specific agonists for peroxisomal proliferator activated receptor gamma and retinoic acid X receptors. J. Biol. Chem. 280 (2005) 38317-38327
26. Luci S., Giemsa B., Kluge H., and Eder K. Clofibrate causes an upregulation of PPAR-{alpha} target genes but does not alter expression of SREBP target genes in liver and adipose tissue of pigs. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293 (2007) R70-R77
27. Mandard S., Muller M., and Kersten S. Peroxisome proliferator-activated receptor alpha target genes. Cell. Mol. Life Sci. 61 (2004) 393-416
28. Mossman T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65 (1983) 55-63
29. Naderali E.K., Fatani S., and Williams G. Fenofibrate lowers adiposity and corrects metabolic abnormalities, but only partially restores endothelial function in dietary obese rats. Atherosclerosis 177 (2004) 307-312
30. Pfaffl M.W. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29 (2001) e45
31. Quinn C.E., Hamilton P.K., Lockhart C.J., and McVeigh G.E. Thiazolidinediones: effects on insulin resistance and the cardiovascular system. Br. J. Pharmacol. 153 (2008) 636-645
32. Schadinger S.E., Bucher N.L., Schreiber B.M., and Farmer S.R. PPARgamma2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes. Am. J. Physiol. Endocrinol. Metab. 288 (2005) E1195-E1205
33. Schoonjans K., Staels B., and Auwerx J. Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J. Lipid Res. 37 (1996) 907-925
34. Schoonjans K., Martin G., Staels B., and Auwerx J. Peroxisome proliferator-activated receptors, orphans with ligands and functions. Curr. Opin. Lipidol. 8 (1997) 159-166
35. Sekiya M., Yahagi N., Matsuzaka T., Najima Y., Nakakuki M., Nagai R., Ishibashi S., Osuga J., Yamada N., and Shimano H. Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Hepatology 38 (2003) 1529-1539
36. Sever N., Song B.L., Yabe D., Goldstein J.L., Brown M.S., and DeBose-Boyd R.A. Insig-dependent ubiquitination and degradation of mammalian 3-hydroxy-3-methylglutaryl-CoA reductase stimulated by sterols and geranylgeraniol. J. Biol. Chem. 278 (2003) 52479-52490
37. Shimomura I., Shimano H., Horton J.D., Goldstein J.L., and Brown M.S. Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells. J. Clin. Invest. 99 (1997) 838-845
38. Staels B., Dallongeville J., Auwerx J., Schoonjans K., Leitersdorf E., and Fruchart J.C. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation 98 (1998) 2088-2093
39. Yabe D., Brown M.S., and Goldstein J.L. Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 12753-12758
40. Yabe D., Komuro R., Liang G., Goldstein J.L., and Brown M.S. Liver-specific mRNA for Insig-2 down-regulated by insulin: implications for fatty acid synthesis. Proc. Natl. Acad. Sci. U.S.A. 100 (2003) 3155-3160
41. Yahagi N., Shimano H., Hasty A.H., Amemiya-Kudo M., Okazaki H., Tamura Y., Iizuka Y., Shionoiri F., Ohashi K., Osuga J., Harada K., Gotoda T., Nagai R., Ishibashi S., and Yamada N. A crucial role of sterol regulatory element-binding protein-1 in the regulation of lipogenic gene expression by polyunsaturated fatty acids. J. Biol. Chem. 274 (1999) 35840-35844
42. Yang T., Espenshade P.J., Wright M.E., Yabe D., Gong Y., Aebersold R., Goldstein J.L., and Brown M.S. Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell 110 (2002) 489-500
43. Yoshikawa T., Ide T., Shimano H., Yahagi N., Amemiya-Kudo M., Matsuzaka T., Yatoh S., Kitamine T., Okazaki H., Tamura Y., Sekiya M., Takahashi A., Hasty A.H., Sato R., Sone H., Osuga J., Ishibashi S., and Yamada N. Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. I. PPARs suppress sterol regulatory element binding protein-1c promoter through inhibition of LXR signaling. Mol. Endocrinol. 17 (2003) 1240-1254
44. Yu-Poth S., Yin D., Kris-Etherton P.M., Zhao G., and Etherton T.D. Long-chain polyunsaturated fatty acids upregulate LDL receptor protein expression in fibroblasts and HepG2 cells. J. Nutr. 135 (2005) 2541-2545
45. Zimetbaum P., Frishman W.H., and Kahn S. Effects of gemfibrozil and other fibric acid derivatives on blood lipids and lipoproteins. J. Clin. Pharmacol. 31 (1991) 25-37