n-3 LCPUFA in the reversal of hepatic steatosis: the role of ACOX and CAT-1
DOI:
https://doi.org/10.3989/gya.0886152Keywords:
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), ReversionAbstract
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.
Downloads
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
How to Cite
Issue
Section
License
Copyright (c) 2016 Consejo Superior de Investigaciones Científicas (CSIC)
This work is licensed under a Creative Commons Attribution 4.0 International License.
© CSIC. Manuscripts published in both the print and online versions of this journal are the property of the Consejo Superior de Investigaciones Científicas, and quoting this source is a requirement for any partial or full reproduction.
All contents of this electronic edition, except where otherwise noted, are distributed under a Creative Commons Attribution 4.0 International (CC BY 4.0) licence. You may read the basic information and the legal text of the licence. The indication of the CC BY 4.0 licence must be expressly stated in this way when necessary.
Self-archiving in repositories, personal webpages or similar, of any version other than the final version of the work produced by the publisher, is not allowed.
