n-3 LCPUFA in the reversal of hepatic steatosis: the role of ACOX and CAT-1

Authors

  • G. S. Tapia Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile
  • D. González-Mañán Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile
  • A. D’Espessailles Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile
  • C. G. Dossi Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile

DOI:

https://doi.org/10.3989/gya.0886152

Keywords:

ACOX (Acyl coenzyme A oxidase), AP-1(activating protein 1), CAT-1 (carnitine acyl transferase I), HFD (high fat diet), NAFLD (non-alcoholic fatty liver disease), n-3 LCPUFA (n-3 long chain polyunsaturated fatty acid), Reversion

Abstract


The aim of this study was to investigate the roles of the Acyl co-enzyme A oxidase (ACOX), carnitine acyl transferase I (CAT-1) and activating protein 1 (AP-1) in the reversal of hepatic steatosis with dietary change and n-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation. Male C57BL/6J mice were given either a control diet (CD) or a high fat diet (HFD) for 12 weeks, and then continued with the CD or CD plus n-3 LCPUFA for eight weeks. After this period, body and adipose visceral tissue weight were analyzed and liver samples were taken to measure ACOX, CAT-1 and c-jun levels. The dietary change from HFD to a norm caloric diet plus n-3 LCPUFA supplementation significantly reduced liver steatosis and adipose tissue: body weight ratio, along with an increase in the hepatic ACOX and CAT-1 levels and normalization of AP-1 expression that could favor the fatty acid beta-oxidation over lipogenesis and regulate inflammation. These results provide new data on the enzymatic metabolism underlying dietary change to a norm caloric diet plus n-3 LCPUFA supplementation.

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References

Adams LA, Angulo P and Lindor KD. 2005. Nonalcoholic fatty liver disease. Can. Med. Assoc. J. 172, 899–905. http://dx.doi.org/10.1503/cmaj.045232 PMid:15795412 PMCid:PMC554876

Angel P, Hattori K, Smeal T and Karin M. 1988. The jun proto-oncogene is positively autoregulated by its product, jun/AP-1. Cell. 55, 875–885. http://dx.doi.org/10.1016/0092-8674(88)90143-2

Araya J, Rodrigo R, Pettinelli P, Araya V, Poniachik J and Videla L. 2010. Decreased liver fatty acid ?-6 and ?-5 desaturase activity in obese patients. Obesity. 18, 1460–1463. http://dx.doi.org/10.1038/oby.2009.379 PMid:19875987

Araya J, Rodrigo R, Videla L, Thielemann L, Orellana M, Pettinelli P and Poniachik J. 2004. Increase in long-chain polyunsaturated fatty acid n-6/n-3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease. Clin. Sci. 106, 635–643. http://dx.doi.org/10.1042/CS20030326 PMid:14720121

Aronis A, Madar Z and Tirosh O. 2005. Mechanism underlying oxidative stress-mediated lipotoxicity: Exposure of J774.2 to macrophages triacylglycerols facilitates mitochondrial reactive oxygen species production and cellular necrosis. Free Radic. Biol. Med. 38, 1221–1230. http://dx.doi.org/10.1016/j.freeradbiomed.2005.01.015 PMid:15808420

Baffy G. 2009. Kupffer cells in non-alcoholic fatty liver disease: The emerging view. J. Hepatol. 51, 212–223. http://dx.doi.org/10.1016/j.jhep.2009.03.008 PMid:19447517 PMCid:PMC2694233

Bartlett K and Eaton S. 2004. Mitochondrial ?-oxidation. Eur. J. Biochem. 271, 462–469. http://dx.doi.org/10.1046/j.1432-1033.2003.03947.x PMid:14728673

Bellentani S, Scaglioni F, Marino M and Bedogni G. 2010. Epidemiology of non-alcoholic fatty liver disease (NAFLD). Dig Dis. 28, 155–161. http://dx.doi.org/10.1159/000282080 PMid:20460905

Brunt EM, Janney CG, Di Biscegle AM, Neuschwander-Tetri BA and Bacon BR. 1999. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am. J. Gastroenterol. 94, 2467–2474. http://dx.doi.org/10.1111/j.1572-0241.1999.01377.x PMid:10484010

Delerive P, Fruchart JC and Staels B. 2001. Peroxisome proliferator-activated receptors ininflamation control. J. Endocrinology. 169, 453–459. http://dx.doi.org/10.1677/joe.0.1690453 PMid:11375115

De Roos B, Mavrommatis Y and Brouwer I. 2009. Longchain n-3 polyunsaturated fatty acids: new insights into mechanisms relating to inflammation and coronary heart disease. Br. J. Pharmacol. 158, 413–428. http://dx.doi.org/10.1111/j.1476-5381.2009.00189.x PMid:19422375 PMCid:PMC2757681

De Meijer V, Le H, Meisel J, Sharif M, Pan A, Nos. V and Puder M. 2010. Dietary fat intake promotes the development of hepatic steatosis independently from excess caloric consumption in a murine model. Metabolism. 59, 1092–105. http://dx.doi.org/10.1016/j.metabol.2009.11.006 PMid:20060143 PMCid:PMC3361716

Dorn C, Engelmann J, Saugspier M, Koch A, Hartmann A, Müller M, Spang R, Bossenhorff A and Hellerbrand C. 2014. Increased expression of c-Jun in nonalcoholic fatty liver disease. Lab Invest. 94, 394–408. http://dx.doi.org/10.1038/labinvest.2014.3 PMid:24492282

Dossi CG, Tapia GS, Espinosa A, Videla LA and D'Espessailles A. 2014. Reversal of High-fat diet-induced hepatic steatosis by n-3 LCPUFA: role of PPAR-? and SREBP-1c. J. Nutr. Biochem. 25, 977–984. http://dx.doi.org/10.1016/j.jnutbio.2014.04.011 PMid:24993917

Dowman JK, Tomlinson JW and Newsome PN. 2010. Pathogenesis of non-alcoholic fatty liver disease. Int. J. Med. 103, 71–83. http://dx.doi.org/10.1093/qjmed/hcp158

Fernandez-Sanchez A, Madrigal-Santillan E, Bautista M, Esquivel-Soto J, Morales-Gonzalez A, and Esquivel-Chirino C. 2011. Inflammation, Oxidative Stress, and Obesity. Int J Mol Sci. 12, 3117–32. http://dx.doi.org/10.3390/ijms12053117 PMid:21686173 PMCid:PMC3116179

Hasenfuss SC, Bakiri L, Thomsen M, Williams E, Auwerx J and Wagner E. 2014. Regulation of Steatohepatitis and PPAR? Signaling by Distinct AP-1 Dimers. Cell Metabolism. 19, 84–95. http://dx.doi.org/10.1016/j.cmet.2013.11.018 PMid:24411941 PMCid:PMC4023468

Hong S, Gronert K, Devchand PR, Moussignac RL and Serhan CN. 2003. Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells: Autacoids in anti-inflammation. J. Biol. Chem. 278, 14677–14687. http://dx.doi.org/10.1074/jbc.M300218200 PMid:12590139

Houstis N, Rosen E and Lander E. 2006. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440, 944–948. http://dx.doi.org/10.1038/nature04634 PMid:16612386

Inoue M, Ohtake T, Motomura W, Takahashi N, Hosoki Y, Miyoshi S, Suzuki Y, Saito H, Kohgo Y and Okumura T. 2005. Increased expression of PPAR? in high fat dietinduced liver steatosis in mice. Bioch and Bioph Res Comms. 336, 215–222. http://dx.doi.org/10.1016/j.bbrc.2005.08.070 PMid:16125673

Leamy AK, Egnatchik RA and Young JD. 2013. Molecular Mechanisms and the Role of Saturated Fatty Acids in the Progression of Non-Alcoholic Fatty Liver Disease. Prog Lipid Res. 52:165–174. http://dx.doi.org/10.1016/j.plipres.2012.10.004 PMid:23178552 PMCid:PMC3868987

Malaguarnera M, Di Rosa M, Nicoletti F, Malaguarnera L. 2009. Molecular mechanisms involved in NAFLD progression. J. Mol. Med. 87, 679–695. http://dx.doi.org/10.1007/s00109-009-0464-1 PMid:19352614

Michalik L, Auwerx J, Berger JP, Chatterjee VK, Glass CK, Gonzalez FJ, et al. 2006. International Union of Pharmacology. LXI. Peroxisome Proliferator-Activated Receptors. Pharmacol Rev. 58, 726–741. http://dx.doi.org/10.1124/pr.58.4.5 PMid:17132851

Musso G, Gambino G, and Cassader M. 2009. Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD). Prog. in Lipid Research. 48, 1–26. http://dx.doi.org/10.1016/j.plipres.2008.08.001 PMid:18824034

Nobili V and Sanyal AJ. 2012. Treatment of nonalcoholic fatty liver disease in adults and children: closer look at the arsenal. J. Gastroenterol. 47, 29–36. http://dx.doi.org/10.1007/s00535-011-0467-x PMid:21983927

Poirier Y, Antonenkov VD, Glumoff T and Hiltunen JK. 2006. Peroxisomal ?-oxidation: A metabolic pathway with multiple functions. Mol Cell Res. 1763, 1413–1426. http://dx.doi.org/10.1016/j.bbamcr.2006.08.034

Shapiro H, Tehilla M, Attal-Singer J, Bruck R, Luzzatti R and Singer P. 2011. The therapeutic potential of longchain omega-3 fatty acids in nonalcoholic fatty liver disease. Clin Nutr. 30, 6–19. http://dx.doi.org/10.1016/j.clnu.2010.06.001 PMid:20619513

Surwit RS, Kuhn CM, Cochrane C, McCubbin JA and Feinglos MN. 1988. Diet-induced type II diabetes in C57BL/6J mice. Diabetes. 37, 1163–1167. http://dx.doi.org/10.2337/diab.37.9.1163 PMid:3044882

Thanos D, Georgopoulos K, Greenberg M and Leder P. 1988. c-jun dimerizes with itself and with c-fos, forming complexes of different DNA binding affinities. Cell. 55, 917–924. http://dx.doi.org/10.1016/0092-8674(88)90147-X

Valenzuela R and Videla L. 2011. The importance of the long-chain polyunsaturated fatty acid n-6/n-3 ratio in development of non-alcoholic fatty liver associated with obesity. Food Funct. 2, 644–648. http://dx.doi.org/10.1039/c1fo10133a PMid:22008843

Valenzuela R, Espinosa A, Gonz.lez D, Fern.ndez V, Videla LA, Romanque P, et al. 2012. N-3 long-chain polyunsaturated fatty acid supplementation significantly reduces liver oxidative stress in high fat induced steatosis. Plos One. 7, e46400. http://dx.doi.org/10.1371/journal.pone.0046400 PMid:23082120 PMCid:PMC3474802

Videla L and Pettinelli P. 2012. Misregulation of PPAR functioning and its pathogenic consequences associated with nonalcoholic fatty liver disease in human obesity. PPAR Res. 2012, 1–14. http://dx.doi.org/10.1155/2012/107434 PMid:23304111 PMCid:PMC3526338

Ye D, Zhang D, Oltman C, Dellsperger K, Lee HC and Van Rollins M. 2002. Cytochrome P-450 epoxygenase metabolites of docosahexaenoate potently dilate coronary arterioles by activating large-conductance calcium-activated potassium channels. J. Pharmacol. Exp. Ther. 303. http://dx.doi.org/10.1124/jpet.303.2.768

Published

2016-06-30

How to Cite

1.
Tapia GS, González-Mañán D, D’Espessailles A, Dossi CG. n-3 LCPUFA in the reversal of hepatic steatosis: the role of ACOX and CAT-1. grasasaceites [Internet]. 2016Jun.30 [cited 2022Dec.4];67(2):e134. Available from: https://grasasyaceites.revistas.csic.es/index.php/grasasyaceites/article/view/1600

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Research