Eicosapentaenoic acid improves hepatic steatosis independent of PPARα activation through inhibition of SREBP-1 maturation in mice

Biochemical Pharmacology

Volumn 80, Issue 10, 2010, Pages 1601-1612

  Tanaka, Naoki ^a,b   Zhang, Xiuguo ^a   Sugiyama, Eiko ^c   Kono, Hiroyuki ^d   Horiuchi, Akira ^e   Nakajima, Takero ^a   Kanbe, Hiroki ^a   Tanaka, Eiji ^b   Gonzalez, Frank J ^f   Aoyama, Toshifumi ^a  

^a SHINSHU UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^b SHINSHU UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^c Nagano Prefectural College   (Japan)

^d Mochida Pharmaceutical Company Limited   (Japan)

^e Showa Inan General Hospital   (Japan)

^f NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Oxidation; Fatty acid uptake; S1P; SCAP; Superoxide dismutase

Indexed keywords

ICOSAPENTAENOIC ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; SUPEROXIDE DISMUTASE; FAT INTAKE; FENOFIBRATE; SREBF1 PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; DOWN REGULATION; DRUG BINDING; DRUG EFFECT; FATTY ACID OXIDATION; FATTY ACID TRANSPORT; FATTY LIVER; GENOTYPE; HYDROLYSIS; LIPID DIET; LIPID LIVER LEVEL; LIPID TRANSPORT; LIPOGENESIS; MALE; MOUSE; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; ANIMAL; ANTAGONISTS AND INHIBITORS; DISEASE MODEL; DRUG EFFECTS; FAT INTAKE; GENETICS; IMMUNOBLOTTING; KNOCKOUT MOUSE; LIPID PEROXIDATION; LIVER; LIVER FUNCTION TEST; METABOLISM; PATHOLOGY;

ANIMALS; DIETARY FATS; DISEASE MODELS, ANIMAL; EICOSAPENTAENOIC ACID; FATTY LIVER; GENOTYPE; IMMUNOBLOTTING; LIPID PEROXIDATION; LIVER; LIVER FUNCTION TESTS; MALE; MICE; MICE, KNOCKOUT; OXIDATIVE STRESS; PPAR ALPHA; PROCETOFEN; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; FENOFIBRATE;

EID: 77957020446     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bcp.2010.07.031     Document Type: Article

References (47)

1. Farrell G.C., Larter C.Z. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 2006, 43:S99-S112.
2. de Alwis N.M., Day C.P. Non-alcoholic fatty liver disease: the mist gradually clears. J Hepatol 2008, 48:S104-S112.
3. Ekstedt M., Franzen L.E., Mathiesen U.L., Thorelius L., Holmqvist M., Bodemar G., et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006, 44:865-873.
4. Nagaya T., Tanaka N., Komatsu M., Ichijo T., Sano K., Horiuchi A., et al. Development from simple steatosis to liver cirrhosis and hepatocellular carcinoma: a 27-year follow-up case. Clin J Gastroenterol 2008, 1:116-121.
5. Vuppalanchi R., Chalasani N. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management. Hepatology 2009, 49:306-317.
6. Dyeberg J., Bang H.O. Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. Lancet 1979, 2:433-435.
7. Kromhout D., Bosschieter E.B., de Lezenne Coulander C. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 1985, 312:1205-1209.
8. Lemaitre R.N., King I.B., Mozaffarian D., Kuller L.H., Tracy R.P., Siscovick D.S. N-3 polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study. Am J Clin Nutr 2003, 77:319-325.
9. Yokoyama M., Origasa H., Matsuzaki M., Matsuzawa Y., Saito Y., Ishikawa Y., et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomized open-label, blinded endpoint analysis. Lancet 2007, 369:1090-1098.
10. Svegliati-Baroni G., Candelaresi C., Saccomanno S., Ferretti G., Bachetti T., Marzioni M., et al. A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptor-α and n-3 polyunsaturated fatty acid treatment on liver injury. Am J Pathol 2006, 169:846-860.
11. Capanni M., Calella F., Biagini M.R., Genise S., Raimondi L., Bedogni G., et al. Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study. Aliment Pharmacol Ther 2006, 23:1143-1151.
12. Clarke S.D. Nonalcoholic steatosis and steatohepatitis. I. Molecular mechanism for polyunsaturated fatty acid regulation of gene transcription. Am J Physiol Gastrointest Liver Physiol 2001, 281:G865-G869.
13. Gonzalez F.J., Shah Y.M. PPARα: mechanism of species differences and hepatocarcinogenesis of peroxisome proliferators. Toxicology 2008, 246:2-8.
14. Ferre P., Foufelle F. SREBP-1c transcription factor and lipid homeostasis: clinical perspective. Horm Res 2007, 68:72-82.
15. Forman B.M., Chen J., Evans R.M. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors α and δ. Proc Natl Acad Sci U S A 1997, 94:4312-4317.
16. Yoshikawa T., Shimano H., Yahagi N., Ide T., Amemiya-Kudo M., Matsuzaka T., et al. Polyunsaturated fatty acids suppress sterol regulatory element-binding protein 1c promoter activity by inhibition of liver X receptor (LXR) binding to LXR response elements. J Biol Chem 2002, 277:1705-1711.
17. Pawer A., Jump D.B. Unsaturated fatty acid regulation of peroxisome proliferator-activated receptor α activity in rat primary hepatocytes. J Biol Chem 2003, 278:35931-35939.
18. Ren B., Thelen A.P., Peters J.M., Gonzalez F.J., Jump D.B. Polyunsaturated fatty acid suppression of hepatic fatty acid synthase and S14 gene expression does not require peroxisome proliferator-activated receptor α. J Biol Chem 1997, 272:26827-26832.
19. Kim H.J., Takahashi M., Ezaki O. Fish oil feeding decreases mature sterol regulatory element-binding protein 1 (SREBP-1) by down-regulation of SREBP-1c mRNA in mouse liver. A possible mechanism for down-regulation of lipogenic enzyme mRNAs. J Biol Chem 1999, 274:25892-25898.
20. Takahashi M., Tsuboyama-Kasaoka N., Nakatani T., Ishii M., Tsutsumi S., Aburatani H., et al. Fish oil feeding alters liver gene expressions to defend against PPARα activation and ROS production. Am J Physiol Gastrointest Liver Physiol 2002, 282:G338-G348.
21. Dallongeville J., Bauge E., Tailleux A., Peters J.M., Gonzalez F.J., Fruchart J.C., et al. Peroxisome proliferator-activated receptor α is not rate-limiting for the lipoprotein-lowering action of fish oil. J Biol Chem 2001, 276:4634-4639.
22. Lee S.S., Pineau T., Drago J., Lee E.J., Owens J.W., Kroetz D.L., et al. Targeted disruption of the α isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol 1995, 15:3012-3022.
23. Tanaka N., Hora K., Makishima H., Kamijo Y., Kiyosawa K., Gonzalez F.J., et al. In vivo stabilization of nuclear retinoid X receptor α in the presence of peroxisome proliferator-activated receptor α. FEBS Lett 2003, 543:120-124.
24. Tanaka N., Moriya K., Kiyosawa K., Koike K., Aoyama T. Hepatitis C virus core protein induces spontaneous and persistent activation of peroxisome proliferator-activated receptor α in transgenic mice: implications for HCV-associated hepatocarcinogenesis. Int J Cancer 2008, 122:124-131.
25. Aoyama T., Yamano S., Waxman D.J., Lapenson D.P., Meyer U.A., Fischer V., et al. Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver. CDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine. J Biol Chem 1989, 264:10388-10395.
26. Aoyama T., Uchida Y., Kelley R.I., Marble M., Hofman K., Tonsgard J.H., et al. A novel disease with deficiency of mitochondrial very-long-chain acyl-CoA dehydrogenase. Biochem Biophys Res Commun 1993, 191:1369-1372.
27. Aoyama T., Souri M., Ushikubo S., Kamijo T., Yamaguchi S., Kelley R.I., et al. Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients. J Clin Invest 1995, 95:2465-2473.
28. Aoyama T., Peters J.M., Iritani N., Nakajima T., Furihata K., Hashimoto T., et al. Altered constitutive expression of fatty acid-metabolizing enzymes in mice lacking the peroxisome proliferator-activated receptor α (PPARα). J Biol Chem 1998, 273:5678-5684.
29. Nakajima T., Tanaka N., Sugiyama E., Kamijo Y., Hara A., Hu R., et al. Cholesterol-lowering effect of bezafibrate is independent of peroxisome proliferator-activated receptor activation in mice. Biochem Pharmacol 2008, 76:108-119.
30. Nakajima T., Tanaka N., Kanbe H., Hara A., Kamijo Y., Zhang X., et al. Bezafibrate at clinically-relevant doses decreases serum/liver triglycerides via down-regulation of SREBP-1c in mice: a novel PPARα-independent mechanism. Mol Pharmacol 2009, 75:782-792.
31. Folch J., Lees M., Sloane Stanley G.H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957, 226:497-509.
32. Okiyama W., Tanaka N., Nakajima T., Tanaka E., Kiyosawa K., Gonzalez F.J., et al. Polyenephosphatidylcholine prevents alcoholic liver disease in PPARα-null mice through attenuation of increases in oxidative stress. J Hepatol 2009, 50:1236-1246.
33. Tanaka N., Moriya K., Kiyosawa K., Koike K., Gonzalez F.J., Aoyama T. PPARα activation is essential for HCV core protein-induced hepatic steatosis and hepatocellular carcinoma in mice. J Clin Invest 2008, 119:683-694.
34. Finck B.N., Kelly D.P. PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. J Clin Invest 2006, 116:615-622.
35. Ma K.L., Ruan X.Z., Powis S.H., Chen Y., Moorhead J.F., Varghese Z. Inflammatory stress exacerbates lipid accumulation in hepatic cells and fatty livers of apolipoprotein E knockout mice. Hepatology 2008, 48:770-781.
36. Browning J.D., Horton J.D. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 2004, 114:147-152.
37. Sekiya M., Yahagi N., Matsuzaka T., Najima Y., Nakakuki M., Nagai R., et al. Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Hepatology 2003, 38:1529-1539.
38. Ishii H., Horie Y., Ohshima S., Anezaki Y., Kinoshita N., Dohmen T., et al. Eicosapentaenoic acid ameliorates steatohepatitis and hepatocellular carcinoma in hepatocyte-specific Pten-deficient mice. J Hepatol 2009, 50:562-571.
39. Sethi S., Ziouzenkova O., Ni H., Wagner D.D., Plutzky J., Mayadas T.N. Oxidized omega-3 fatty acids in fish oil inhibit leukocyte-endothelial interactions through activation of PPARα. Blood 2002, 100:1340-1346.
40. Nakajima T., Iwaki K., Kodama T., Inazawa J., Emi M. Genomic structure and chromosomal mapping of the human site-1 protease (S1P) gene. J Hum Genet 2000, 45:212-217.
41. Schroeder F., Jolly C.A., Cho T.H., Frolov A. Fatty acid binding protein isoforms: structure and function. Chem Phys Lipids 1998, 92:1-25.
42. Greco D., Kotronen A., Westerbacka J., Puig O., Arkkila P., Kiviluoto T., et al. Gene expression in human NAFLD. Am J Physiol Gastrointest Liver Physiol 2008, 294:G1281-G1287.
43. Kwak M.K., Wakabayashi N., Itoh K., Motohashi H., Yamamoto M., Kensler T.W. Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survival. J Biol Chem 2003, 278:8135-8145.
44. Gao R., Wang J., Sekhar K.R., Yin H., Yared N.F., Schneider S.N., et al. Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3. J Biol Chem 2007, 282:2529-2537.
45. Allard J.P., Aghdassi E., Mohammed S., Raman M., Avand G., Arendt B.M., et al. Nutritional assessment and hepatic fatty acid composition in non-alcoholic fatty liver disease (NAFLD): A cross-sectional study. J Hepatol 2008, 48:300-307.
46. Tanaka N., Sano K., Horiuchi A., Tanaka E., Kiyosawa K., Aoyama T. Highly purified eicosapentaenoic acid treatment improves nonalcoholic steatohepatitis. J Clin Gastroenterol 2008, 42:413-418.
47. Nakajima T., Kamijo Y., Tanaka N., Sugiyama E., Tanaka E., Kiyosawa K., et al. Peroxisome proliferator-activated receptor α protects against alcohol-induced liver damage. Hepatology 2004, 40:972-980.