Targeting n-3 Polyunsaturated Fatty Acids in Non-Alcoholic Fatty Liver Disease

Author(s): Rodrigo Valenzuela*, Macarena Ortiz, María Catalina Hernández-Rodas, Francisca Echeverría, Luis Alberto Videla

Journal Name: Current Medicinal Chemistry

Volume 27 , Issue 31 , 2020


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Abstract:

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by abnormal hepatic accumulation of triacylglycerides in the absence of alcohol consumption, in association with Oxidative Stress (OS), a pro-inflammatory state and Insulin Resistance (IR), which are attenuated by n-3 long-chain polyunsaturated Fatty Acids (FAs) C20-C22 (LCPUFAs) supplementation. Main causes of NAFLD comprise high caloric intake and a sedentary lifestyle, with high intakes of saturated FAs.

Methods: The review includes several searches considering the effects of n-3 LCPUFAs in NAFLD in vivo and in vitro models, using the PubMed database from the National Library of Medicine- National Institutes of Health.

Result: The LCPUFAs eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n- 3, DHA) have a positive effect in diminishing liver steatosis, OS, and the levels of aspartate aminotransferase, alanine aminotransferase and pro-inflammatory cytokines, with improvement of insulin sensitivity and adiponectin levels. The molecular pathways described for n-3 LCPUFAs in cellular and animal models and humans include peroxisome proliferator–activated receptor-α activation favouring FA oxidation, diminution of lipogenesis due to sterol responsive element binding protein-1c downregulation and inflammation resolution. Besides, nuclear factor erythroid-2-related factor-2 activation is elicited by n-3 LCPUFA-derived oxidation products producing direct and indirect antioxidant responses, with concomitant anti-fibrogenic action.

Conclusion: The discussed effects of n-3 LCPUFA supplementation support its use in NAFLD, although having a limited value in NASH, a contention that may involve n-3 LCPUFA oxygenated derivatives. Clinical trials establishing optimal dosages, intervention times, type of patients and possible synergies with other natural products are needed in future studies.

Keywords: Liver steatosis, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, anti-lipogenic mechanism.

[1]
Younossi, Z.M.; Loomba, R.; Anstee, Q.M.; Rinella, M.E.; Bugianesi, E.; Marchesini, G.; Neuschwander-Tetri, B.A.; Serfaty, L.; Negro, F.; Caldwell, S.H.; Ratziu, V.; Corey, K.E.; Friedman, S.L.; Abdelmalek, M.F.; Harrison, S.A.; Sanyal, A.J.; Lavine, J.E.; Mathurin, P.; Charlton, M.R.; Goodman, Z.D.; Chalasani, N.P.; Kowdley, K.V.; George, J.; Lindor, K. Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis. Hepatology, 2018, 68(1), 349-360.
[http://dx.doi.org/10.1002/hep.29721] [PMID: 29222917]
[2]
Said, A.; Ghufran, A. Epidemic of non-alcoholic fatty liver disease and hepatocellular carcinoma. World J. Clin. Oncol., 2017, 8(6), 429-436.
[http://dx.doi.org/10.5306/wjco.v8.i6.429] [PMID: 29291167]
[3]
Sberna, A.L.; Bouillet, B.; Rouland, A.; Brindisi, M.C.; Nguyen, A.; Mouillot, T.; Duvillard, L.; Denimal, D.; Loffroy, R.; Vergès, B.; Hillon, P.; Petit, J.M. European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO). Clinical practice recommendations for the management of non-alcoholic fatty liver disease: evaluation of their application in people with type 2 diabetes. Diabet. Med., 2018, 35(3), 368-375.
[http://dx.doi.org/10.1111/dme.13565] [PMID: 29247558]
[4]
Araya, J.; Rodrigo, R.; Videla, L.A.; Thielemann, L.; Orellana, M.; Pettinelli, P.; Poniachik, J. 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. (Lond.), 2004, 106(6), 635-643.
[http://dx.doi.org/10.1042/CS20030326] [PMID: 14720121]
[5]
Poudyal, H.; Panchal, S.K.; Diwan, V.; Brown, L. Omega-3 fatty acids and metabolic syndrome: effects and emerging mechanisms of action. Prog. Lipid Res., 2011, 50(4), 372-387.
[http://dx.doi.org/10.1016/j.plipres.2011.06.003] [PMID: 21762726]
[6]
Barceló-Coblijn, G.; Murphy, E.J. Alpha-linolenic acid and its conversion to longer chain n-3 fatty acids: benefits for human health and a role in maintaining tissue n-3 fatty acid levels. Prog. Lipid Res., 2009, 48(6), 355-374.
[http://dx.doi.org/10.1016/j.plipres.2009.07.002] [PMID: 19619583]
[7]
Rincón-Cervera, M.A.; Valenzuela, R.; Hernandez-Rodas, M.C.; Barrera, C.; Espinosa, A.; Marambio, M.; Valenzuela, A. Vegetable oils rich in alpha linolenic acid increment hepatic n-3 LCPUFA, modulating the fatty acid metabolism and antioxidant response in rats. Prostaglandins Leukot. Essent. Fatty Acids, 2016, 111, 25-35.
[http://dx.doi.org/10.1016/j.plefa.2016.02.002] [PMID: 26995676]
[8]
Metherel, A.H.; Domenichiello, A.F.; Kitson, A.P.; Hopperton, K.E.; Bazinet, R.P. Whole-body DHA synthesis-secretion kinetics from plasma eicosapentaenoic acid and alpha-linolenic acid in the free-living rat. Biochim. Biophys. Acta, 2016, 1861(9 Pt A), 997-1004.
[http://dx.doi.org/10.1016/j.bbalip.2016.05.014] [PMID: 27263420]
[9]
Nakamura, M.T.; Nara, T.Y. Structure, function and dietary regulation of delta6, delta5, and delta9 desaturases. Annu. Rev. Nutr., 2004, 24, 345-376.
[http://dx.doi.org/10.1146/annurev.nutr.24.121803.063211] [PMID: 15189125]
[10]
Valenzuela, R.; Barrera, C.; Espinosa, A.; Llanos, P.; Orellana, P.; Videla, L.A. Reduction in the desaturation capacity of the liver in mice subjected to high fat diet: relation to LCPUFA depletion in liver and extrahepatic tissues. Prostaglandins Leukot. Essent. Fatty Acids, 2015, 98, 7-14.
[http://dx.doi.org/10.1016/j.plefa.2015.04.002] [PMID: 25910408]
[11]
Valenzuela, R.; Echeverria, F.; Ortiz, M.; Rincón-Cervera, M.A.; Espinosa, A.; Hernandez-Rodas, M.C.; Illesca, P.; Valenzuela, A.; Videla, L.A. Hydroxytyrosol prevents reduction in liver activity of Δ-5 and Δ-6 desaturases, oxidative stress, and depletion in long chain polyunsaturated fatty acid content in different tissues of high-fat diet fed mice. Lipids Health Dis., 2017, 16(1), 64.
[http://dx.doi.org/10.1186/s12944-017-0450-5] [PMID: 28395666]
[12]
Valenzuela, R.; Rincón-Cervera, M.A.; Echeverría, F.; Barrera, C.; Espinosa, A.; Hernández-Rodas, M.C.; Ortiz, M.; Valenzuela, A.; Videla, L.A. Iron-induced pro-oxidant and pro-lipogenic responses in relation to impaired synthesis and accretion of long-chain polyunsaturated fatty acids in rat hepatic and extrahepatic tissues. Nutrition, 2018, 45, 49-58.
[http://dx.doi.org/10.1016/j.nut.2017.07.007] [PMID: 29129237]
[13]
Rapoport, S.I.; Igarashi, M.; Gao, F. Quantitative contributions of diet and liver synthesis to docosahexaenoic acid homeostasis. Prostaglandins Leukot. Essent. Fatty Acids, 2010, 82(4-6), 273-276.
[http://dx.doi.org/10.1016/j.plefa.2010.02.015] [PMID: 20226642]
[14]
Rincón-Cervera, M.A.; Valenzuela, R.; Hernandez-Rodas, M.C.; Marambio, M.; Espinosa, A.; Mayer, S.; Romero, N.; Barrera, M.; Sc, C.; Valenzuela, A.; Videla, L.A.; Videla, L.A.; Videla, L.A. Supplementation with antioxidant-rich extra virgin olive oil prevents hepatic oxidative stress and reduction of desaturation capacity in mice fed a high-fat diet: effects on fatty acid composition in liver and extrahepatic tissues. Nutrition, 2016, 32(11-12), 1254-1267.
[http://dx.doi.org/10.1016/j.nut.2016.04.006] [PMID: 27346714]
[15]
Videla, L.A.; Pettinelli, P. Misregulation of PPAR functioning and its pathogenic consequences associated with nonalcoholic fatty liver disease in human obesity. PPAR Res., 2012, 2012 107434
[http://dx.doi.org/10.1155/2012/107434] [PMID: 23304111]
[16]
Pettinelli, P.; Videla, L.A. Up-regulation of PPAR-gamma mRNA expression in the liver of obese patients: an additional reinforcing lipogenic mechanism to SREBP-1c induction. J. Clin. Endocrinol. Metab., 2011, 96(5), 1424-1430.
[http://dx.doi.org/10.1210/jc.2010-2129] [PMID: 21325464]
[17]
Stiede, K.; Miao, W.; Blanchette, H.S.; Beysen, C.; Harriman, G.; Harwood, H.J., Jr; Kelley, H.; Kapeller, R.; Schmalbach, T.; Westlin, W.F. Acetyl-coenzyme A carboxylase inhibition reduces de novo lipogenesis in overweight male subjects: a randomized, double-blind, crossover study. Hepatology, 2017, 66(2), 324-334.
[http://dx.doi.org/10.1002/hep.29246] [PMID: 28470676]
[18]
Gormaz, J.G.; Rodrigo, R.; Videla, L.A.; Beems, M. Biosynthesis and bioavailability of long-chain polyunsaturated fatty acids in non-alcoholic fatty liver disease. Prog. Lipid Res., 2010, 49(4), 407-419.
[http://dx.doi.org/10.1016/j.plipres.2010.05.003] [PMID: 20553760]
[19]
Videla, L.A.; Rodrigo, R.; Araya, J.; Poniachik, J. Oxidative stress and depletion of hepatic long-chain polyunsaturated fatty acids may contribute to nonalcoholic fatty liver disease. Free Radic. Biol. Med., 2004, 37(9), 1499-1507.
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.06.033] [PMID: 15454290]
[20]
Valenzuela, R.; Espinosa, A.; González-Mañán, D.; D’Espessailles, A.; Fernández, V.; Videla, L.A.; Tapia, G. N-3 long-chain polyunsaturated fatty acid supplementation significantly reduces liver oxidative stress in high fat induced steatosis. PLoS One, 2012, 7(10) e46400
[http://dx.doi.org/10.1371/journal.pone.0046400] [PMID: 23082120]
[21]
Echeverría, F.; Ortiz, M.; Valenzuela, R.; Videla, L.A. Long-chain polyunsaturated fatty acids regulation of PPARs, signaling: relationship to tissue development and aging. Prostaglandins Leukot. Essent. Fatty Acids, 2016, 114, 28-34.
[http://dx.doi.org/10.1016/j.plefa.2016.10.001] [PMID: 27926461]
[22]
Horton, J.D.; Goldstein, J.L.; Brown, M.S. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J. Clin. Invest., 2002, 109(9), 1125-1131.
[http://dx.doi.org/10.1172/JCI0215593] [PMID: 11994399]
[23]
Le, H.D.; Meisel, J.A.; de Meijer, V.E.; Gura, K.M.; Puder, M. The essentiality of arachidonic acid and docosahexaenoic acid. Prostaglandins Leukot. Essent. Fatty Acids, 2009, 81(2-3), 165-170.
[http://dx.doi.org/10.1016/j.plefa.2009.05.020] [PMID: 19540099]
[24]
Valenzuela, R.; Espinosa, A.; Llanos, P.; Hernandez-Rodas, M.C.; Barrera, C.; Vergara, D.; Romero, N.; Pérez, F.; Ruz, M.; Videla, L.A. Anti-steatotic effects of an n-3 LCPUFA and extra virgin olive oil mixture in the liver of mice subjected to high-fat diet. Food Funct., 2016, 7(1), 140-150.
[http://dx.doi.org/10.1039/C5FO01086A] [PMID: 26471014]
[25]
McCarthy, E.M.; Rinella, M.E. The role of diet and nutrient composition in nonalcoholic fatty liver disease. J. Acad. Nutr. Diet., 2012, 112(3), 401-409.
[http://dx.doi.org/10.1016/j.jada.2011.10.007] [PMID: 22717200]
[26]
Da Silva, H.E.; Arendt, B.M.; Noureldin, S.A.; Therapondos, G.; Guindi, M.; Allard, J.P. A cross-sectional study assessing dietary intake and physical activity in Canadian patients with nonalcoholic fatty liver disease vs. healthy controls. J. Acad. Nutr. Diet., 2014, 114(8), 1181-1194.
[http://dx.doi.org/10.1016/j.jand.2014.01.009] [PMID: 24631112]
[27]
Hashemi Kani, A.; Alavian, S.M.; Haghighatdoost, F.; Azadbakht, L. Diet macronutrients composition in nonalcoholic fatty liver disease: a review on the related documents. Hepat. Mon., 2014, 14(2) e10939
[http://dx.doi.org/10.5812/hepatmon.10939] [PMID: 24693306]
[28]
Masterton, G.S.; Plevris, J.N.; Hayes, P.C. Review article: omega-3 fatty acids - a promising novel therapy for non-alcoholic fatty liver disease. Aliment. Pharmacol. Ther., 2010, 31(7), 679-692.
[http://dx.doi.org/10.1111/j.1365-2036.2009.04230.x] [PMID: 20415840]
[29]
Zelber-Sagi, S.; Nitzan-Kaluski, D.; Goldsmith, R.; Webb, M.; Blendis, L.; Halpern, Z.; Oren, R. Long term nutritional intake and the risk for non-alcoholic fatty liver disease (NAFLD): a population based study. J. Hepatol., 2007, 47(5), 711-717.
[http://dx.doi.org/10.1016/j.jhep.2007.06.020] [PMID: 17850914]
[30]
Yang, M.; Gong, S.; Ye, S.Q.; Lyman, B.; Geng, L.; Chen, P.; Li, D.Y. Non-alcoholic fatty liver disease in children: focus on nutritional interventions. Nutrients, 2014, 6(11), 4691-4705.
[http://dx.doi.org/10.3390/nu6114691] [PMID: 25353664]
[31]
Araya, J.; Rodrigo, R.; Pettinelli, P.; Araya, A.V.; Poniachik, J.; Videla, L.A. Decreased liver fatty acid delta-6 and delta-5 desaturase activity in obese patients. Obesity (Silver Spring), 2010, 18(7), 1460-1463.
[http://dx.doi.org/10.1038/oby.2009.379] [PMID: 19875987]
[32]
Ter Horst, K.W.; Serlie, M.J. Fructose consumption, lipogenesis and non-alcoholic fatty liver disease. Nutrients, 2017, 9(9), 981.
[http://dx.doi.org/10.3390/nu9090981] [PMID: 28878197]
[33]
Ouyang, X.; Cirillo, P.; Sautin, Y.; McCall, S.; Bruchette, J.L.; Diehl, A.M.; Johnson, R.J.; Abdelmalek, M.F. Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J. Hepatol., 2008, 48(6), 993-999.
[http://dx.doi.org/10.1016/j.jhep.2008.02.011] [PMID: 18395287]
[34]
Siddiqui, R.A.; Xu, Z.; Harvey, K.A.; Pavlina, T.M.; Becker, M.J.; Zaloga, G.P. Comparative study of the modulation of fructose/sucrose-induced hepatic steatosis by mixed lipid formulations varying in unsaturated fatty acid content. Nutr. Metab. (Lond.), 2015, 12, 41.
[http://dx.doi.org/10.1186/s12986-015-0038-x] [PMID: 26583036]
[35]
de Castro, G.S.; Deminice, R.; Simões-Ambrosio, L.M.; Calder, P.C.; Jordão, A.A.; Vannucchi, H. Dietary docosahexaenoic acid and eicosapentaenoic acid influence liver triacylglycerol and insulin resistance in rats fed a high-fructose diet. Mar. Drugs, 2015, 13(4), 1864-1881.
[http://dx.doi.org/10.3390/md13041864] [PMID: 25837985]
[36]
Zhang, C.; Chen, X.; Zhu, R.M.; Zhang, Y.; Yu, T.; Wang, H.; Zhao, H.; Zhao, M.; Ji, Y.L.; Chen, Y.H.; Meng, X.H.; Wei, W.; Xu, D.X. Endoplasmic reticulum stress is involved in hepatic SREBP-1c activation and lipid accumulation in fructose-fed mice. Toxicol. Lett., 2012, 212(3), 229-240.
[http://dx.doi.org/10.1016/j.toxlet.2012.06.002] [PMID: 22698815]
[37]
Zhang, X.; Zhang, J.H.; Chen, X.Y.; Hu, Q.H.; Wang, M.X.; Jin, R.; Zhang, Q.Y.; Wang, W.; Wang, R.; Kang, L.L.; Li, J.S.; Li, M.; Pan, Y.; Huang, J.J.; Kong, L.D. Reactive oxygen species-induced TXNIP drives fructose-mediated hepatic inflammation and lipid accumulation through NLRP3 inflammasome activation. Antioxid. Redox Signal., 2015, 22(10), 848-870.
[http://dx.doi.org/10.1089/ars.2014.5868] [PMID: 25602171]
[38]
Piquet, M.A.; Roulet, M.; Nogueira, V.; Filippi, C.; Sibille, B.; Hourmand-Ollivier, I.; Pilet, M.; Rouleau, V.; Leverve, X.M. Polyunsaturated fatty acid deficiency reverses effects of alcohol on mitochondrial energy metabolism. J. Hepatol., 2004, 41(5), 721-729.
[http://dx.doi.org/10.1016/j.jhep.2004.07.002] [PMID: 15519643]
[39]
Kirk, E.; Reeds, D.N.; Finck, B.N.; Mayurranjan, S.M.; Patterson, B.W.; Klein, S. Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction. Gastroenterology, 2009, 136(5), 1552-1560.
[http://dx.doi.org/10.1053/j.gastro.2009.01.048] [PMID: 19208352]
[40]
Lottenberg, A.M. Afonso, Mda.S.; Lavrador, M.S.; Machado, R.M.; Nakandakare, E.R. The role of dietary fatty acids in the pathology of metabolic syndrome. J. Nutr. Biochem., 2012, 23(9), 1027-1040.
[http://dx.doi.org/10.1016/j.jnutbio.2012.03.004] [PMID: 22749135]
[41]
Cortez-Pinto, H.; Jesus, L.; Barros, H.; Lopes, C.; Moura, M.C.; Camilo, M.E. How different is the dietary pattern in non-alcoholic steatohepatitis patients? Clin. Nutr., 2006, 25(5), 816-823.
[http://dx.doi.org/10.1016/j.clnu.2006.01.027] [PMID: 16677739]
[42]
Zivkovic, A.M.; German, J.B.; Sanyal, A.J. Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease. Am. J. Clin. Nutr., 2007, 86(2), 285-300.
[http://dx.doi.org/10.1093/ajcn/86.2.285] [PMID: 17684197]
[43]
Yaligar, J.; Gopalan, V.; Kiat, O.W.; Sugii, S.; Shui, G.; Lam, B.D.; Henry, C.J.; Wenk, M.R.; Tai, E.S.; Velan, S.S. Evaluation of dietary effects on hepatic lipids in high fat and placebo diet fed rats by in vivo MRS and LC-MS techniques. PLoS One, 2014, 9(3) e91436
[http://dx.doi.org/10.1371/journal.pone.0091436] [PMID: 24638096]
[44]
Shapiro, H.; Tehilla, M.; Attal-Singer, J.; Bruck, R.; Luzzatti, R.; Singer, P. The therapeutic potential of long-chain omega-3 fatty acids in nonalcoholic fatty liver disease. Clin. Nutr., 2011, 30(1), 6-19.
[http://dx.doi.org/10.1016/j.clnu.2010.06.001] [PMID: 20619513]
[45]
Blasbalg, T.L.; Hibbeln, J.R.; Ramsden, C.E.; Majchrzak, S.F.; Rawlings, R.R. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am. J. Clin. Nutr., 2011, 93(5), 950-962.
[http://dx.doi.org/10.3945/ajcn.110.006643] [PMID: 21367944]
[46]
Patterson, E.; Wall, R.; Fitzgerald, G.F.; Ross, R.P.; Stanton, C. Health implications of high dietary omega-6 polyunsaturated fatty acids. J. Nutr. Metab., 2012, 2012 539426
[http://dx.doi.org/10.1155/2012/539426] [PMID: 22570770]
[47]
Pachikian, B.D.; Essaghir, A.; Demoulin, J.B.; Neyrinck, A.M.; Catry, E.; De Backer, F.C.; Dejeans, N.; Dewulf, E.M.; Sohet, F.M.; Portois, L.; Deldicque, L.; Molendi-Coste, O.; Leclercq, I.A.; Francaux, M.; Carpentier, Y.A.; Foufelle, F.; Muccioli, G.G.; Cani, P.D.; Delzenne, N.M. Hepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin resistance in mice: genomic analysis of cellular targets. PLoS One, 2011, 6(8) e23365
[http://dx.doi.org/10.1371/journal.pone.0023365] [PMID: 21853118]
[48]
Simopoulos, A.P. Dietary omega-3 fatty acid deficiency and high fructose intake in the development of metabolic syndrome, brain metabolic abnormalities, and non-alcoholic fatty liver disease. Nutrients, 2013, 5(8), 2901-2923.
[http://dx.doi.org/10.3390/nu5082901] [PMID: 23896654]
[49]
Mager, D.R.; Patterson, C.; So, S.; Rogenstein, C.D.; Wykes, L.J.; Roberts, E.A. Dietary and physical activity patterns in children with fatty liver. Eur. J. Clin. Nutr., 2010, 64(6), 628-635.
[http://dx.doi.org/10.1038/ejcn.2010.35] [PMID: 20216561]
[50]
St-Jules, D.E.; Watters, C.A.; Brunt, E.M.; Wilkens, L.R.; Novotny, R.; Belt, P.; Lavine, J.E. Nonalcoholic steatohepatitis clinical research network. Estimation of fish and ω-3 fatty acid intake in pediatric nonalcoholic fatty liver disease. J. Pediatr. Gastroenterol. Nutr., 2013, 57(5), 627-633.
[http://dx.doi.org/10.1097/MPG.0b013e3182a1df77] [PMID: 24177784]
[51]
Enjoji, M.; Nakamuta, M. Is the control of dietary cholesterol intake sufficiently effective to ameliorate nonalcoholic fatty liver disease? World J. Gastroenterol., 2010, 16(7), 800-803.
[http://dx.doi.org/10.3748/wjg.v16.i7.800]] [PMID: 20143458]
[52]
Ferramosca, A.; Zara, V. Modulation of hepatic steatosis by dietary fatty acids. World J. Gastroenterol., 2014, 20(7), 1746-1755.
[http://dx.doi.org/10.3748/wjg.v20.i7.1746] [PMID: 24587652]
[53]
Kelley, D.S.; Vemuri, M.; Adkins, Y.; Gill, S.H.; Fedor, D.; Mackey, B.E. Flaxseed oil prevents trans-10, cis-12-conjugated linoleic acid-induced insulin resistance in mice. Br. J. Nutr., 2009, 101(5), 701-708.
[http://dx.doi.org/10.1017/S0007114508027451] [PMID: 18710604]
[54]
Costantini, L.; Molinari, R.; Farinon, B.; Merendino, N. Impact of omega-3 fatty acids on the gut microbiota. Int. J. Mol. Sci., 2017, 18(12), 1-18.
[http://dx.doi.org/10.3390/ijms18122645] [PMID: 29215589]
[55]
Videla, L.A.; Rodrigo, R.; Araya, J.; Poniachik, J. Insulin resistance and oxidative stress interdependency in non-alcoholic fatty liver disease. Trends Mol. Med., 2006, 12(12), 555-558.
[http://dx.doi.org/10.1016/j.molmed.2006.10.001] [PMID: 17049925]
[56]
Marchesini, G.; Brizi, M.; Bianchi, G.; Tomassetti, S.; Bugianesi, E.; Lenzi, M.; McCullough, A.J.; Natale, S.; Forlani, G.; Melchionda, N. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes, 2001, 50(8), 1844-1850.
[http://dx.doi.org/10.2337/diabetes.50.8.1844] [PMID: 11473047]
[57]
Charlton, M.R.; Burns, J.M.; Pedersen, R.A.; Watt, K.D.; Heimbach, J.K.; Dierkhising, R.A. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology, 2011, 141(4), 1249-1253.
[http://dx.doi.org/10.1053/j.gastro.2011.06.061] [PMID: 21726509]
[58]
Hooper, A.J.; Adams, L.A.; Burnett, J.R. Genetic determinants of hepatic steatosis in man. J. Lipid Res., 2011, 52(4), 593-617.
[http://dx.doi.org/10.1194/jlr.R008896] [PMID: 21245030]
[59]
Bugianesi, E.; Moscatiello, S.; Ciaravella, M.F.; Marchesini, G. Insulin resistance in nonalcoholic fatty liver disease. Curr. Pharm. Des., 2010, 16(17), 1941-1951.
[http://dx.doi.org/10.2174/138161210791208875] [PMID: 20370677]
[60]
Valenzuela, R.; Videla, L.A. 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., 2011, 2(11), 644-648.
[http://dx.doi.org/10.1039/c1fo10133a] [PMID: 22008843]
[61]
Videla, L.A.; Fernández, V.; Cornejo, P.; Vargas, R.; Carrasco, J.; Fernández, J.; Varela, N. Causal role of oxidative stress in unfolded protein response development in the hyperthyroid state. Free Radic. Biol. Med., 2015, 89, 401-408.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.09.004] [PMID: 26434419]
[62]
Stienstra, R.; Duval, C.; Müller, M.; Kersten, S. PPARs, obesity and inflammation. PPAR Res., 2007, 2007, 95974.
[http://dx.doi.org/10.1155/2007/95974] [PMID: 17389767]
[63]
Berger, J.P.; Akiyama, T.E.; Meinke, P.T. PPARs: therapeutic targets for metabolic disease. Trends Pharmacol. Sci., 2005, 26(5), 244-251.
[http://dx.doi.org/10.1016/j.tips.2005.03.003] [PMID: 15860371]
[64]
Souza-Mello, V. Peroxisome proliferator-activated receptors as targets to treat non-alcoholic fatty liver disease. World J. Hepatol., 2015, 7(8), 1012-1019.
[http://dx.doi.org/10.4254/wjh.v7.i8.1012] [PMID: 26052390]
[65]
Zúñiga, J.; Cancino, M.; Medina, F.; Varela, P.; Vargas, R.; Tapia, G. N-3 PUFA supplementation triggers PPAR-α activation and PPAR-α/NF-κB interaction: anti-inflammatory implications in liver ischemia-reperfusion injury. PLoS One, 2011, 6, 1-10.
[http://dx.doi.org/10.1371/journal.pone.0028502] [PMID: 22174823]
[66]
Marx, N.; Sukhova, G.K.; Collins, T.; Libby, P.; Plutzky, J. PPAR alpha activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Circulation, 1999, 99(24), 3125-3131.
[http://dx.doi.org/10.1161/01.CIR.99.24.3125] [PMID: 10377075]
[67]
Gloire, G.; Legrand-Poels, S.; Piette, J. NF-kappaB activation by reactive oxygen species: fifteen years later. Biochem. Pharmacol., 2006, 72(11), 1493-1505.
[http://dx.doi.org/10.1016/j.bcp.2006.04.011] [PMID: 16723122]
[68]
Videla, L.A.; Tapia, G.; Rodrigo, R.; Pettinelli, P.; Haim, D.; Santibañez, C.; Araya, A.V.; Smok, G.; Csendes, A.; Gutierrez, L.; Rojas, J.; Castillo, J.; Korn, O.; Maluenda, F.; Díaz, J.C.; Rencoret, G.; Poniachik, J. Liver NF-kappaB and AP-1 DNA binding in obese patients. Obesity (Silver Spring), 2009, 17(5), 973-979.
[http://dx.doi.org/10.1038/oby.2008.601] [PMID: 19165171]
[69]
Pettinelli, P.; Del Pozo, T.; Araya, J.; Rodrigo, R.; Araya, A.V.; Smok, G.; Csendes, A.; Gutierrez, L.; Rojas, J.; Korn, O.; Maluenda, F.; Diaz, J.C.; Rencoret, G.; Braghetto, I.; Castillo, J.; Poniachik, J.; Videla, L.A. Enhancement in liver SREBP-1c/PPAR-alpha ratio and steatosis in obese patients: correlations with insulin resistance and n-3 long-chain polyunsaturated fatty acid depletion. Biochim. Biophys. Acta, 2009, 1792(11), 1080-1086.
[http://dx.doi.org/10.1016/j.bbadis.2009.08.015] [PMID: 19733654]
[70]
Videla, L.A. Liver NF-κB and AP-1 activation and PPAR-α expression are negatively correlated in obese patients: pro-inflammatory implications. Clin. Nutr., 2010, 29(5), 687-688.
[http://dx.doi.org/10.1016/j.clnu.2010.03.006] [PMID: 20403650]
[71]
Tailleux, A.; Wouters, K.; Staels, B. Roles of PPARs in NAFLD: potential therapeutic targets. Biochim. Biophys. Acta, 2012, 1821(5), 809-818.
[http://dx.doi.org/10.1016/j.bbalip.2011.10.016] [PMID: 22056763]
[72]
Suzuki, T.; Motohashi, H.; Yamamoto, M. Toward clinical application of the Keap1-Nrf2 pathway. Trends Pharmacol. Sci., 2013, 34(6), 340-346.
[http://dx.doi.org/10.1016/j.tips.2013.04.005] [PMID: 23664668]
[73]
Gao, L.; Wang, J.; Sekhar, K.R.; Yin, H.; Yared, N.F.; Schneider, S.N.; Sasi, S.; Dalton, T.P.; Anderson, M.E.; Chan, J.Y.; Morrow, J.D.; Freeman, M.L. Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3. J. Biol. Chem., 2007, 282(4), 2529-2537.
[http://dx.doi.org/10.1074/jbc.M607622200] [PMID: 17127771]
[74]
Demoz, A.; Willumsen, N.; Berge, R.K. Eicosapentaenoic acid at hypotriglyceridemic dose enhances the hepatic antioxidant defense in mice. Lipids, 1992, 27(12), 968-971.
[http://dx.doi.org/10.1007/BF02535573] [PMID: 1487958]
[75]
Sugimoto, H.; Okada, K.; Shoda, J.; Warabi, E.; Ishige, K.; Ueda, T.; Taguchi, K.; Yanagawa, T.; Nakahara, A.; Hyodo, I.; Ishii, T.; Yamamoto, M. Deletion of nuclear factor-E2-related factor-2 leads to rapid onset and progression of nutritional steatohepatitis in mice. Am. J. Physiol. Gastrointest. Liver Physiol., 2010, 298(2), G283-G294.
[http://dx.doi.org/10.1152/ajpgi.00296.2009] [PMID: 19926817]
[76]
Wakabayashi, N.; Slocum, S.L.; Skoko, J.J.; Shin, S.; Kensler, T.W. When NRF2 talks, who’s listening? Antioxid. Redox Signal., 2010, 13(11), 1649-1663.
[http://dx.doi.org/10.1089/ars.2010.3216] [PMID: 20367496]
[77]
Seldon, M.P.; Silva, G.; Pejanovic, N.; Larsen, R.; Gregoire, I.P.; Filipe, J.; Anrather, J.; Soares, M.P. Heme oxygenase-1 inhibits the expression of adhesion molecules associated with endothelial cell activation via inhibition of NF-kappaB RelA phosphorylation at serine 276. J. Immunol., 2007, 179(11), 7840-7851.
[http://dx.doi.org/10.4049/jimmunol.179.11.7840] [PMID: 18025230]
[78]
Bhaswant, M.; Poudyal, H.; Brown, L. Mechanisms of enhanced insulin secretion and sensitivity with n-3 unsaturated fatty acids. J. Nutr. Biochem., 2015, 26(6), 571-584.
[http://dx.doi.org/10.1016/j.jnutbio.2015.02.001] [PMID: 25841249]
[79]
Mosca, L.; Ballantyne, C.M.; Bays, H.E.; Guyton, J.R.; Philip, S.; Doyle, R.T., Jr; Juliano, R.A. Usefulness of icosapent ethyl (eicosapentaenoic acid ethyl ester) in women to lower triglyceride levels (Results from the MARINE and ANCHOR trials). Am. J. Cardiol., 2017, 119(3), 397-403.
[http://dx.doi.org/10.1016/j.amjcard.2016.10.027] [PMID: 27939227]
[80]
Echeverría, F.; Valenzuela, R.; Catalina Hernandez-Rodas, M.; Valenzuela, A. Docosahexaenoic acid (DHA), a fundamental fatty acid for the brain: new dietary sources. Prostaglandins Leukot. Essent. Fatty Acids, 2017, 124, 1-10.
[http://dx.doi.org/10.1016/j.plefa.2017.08.001] [PMID: 28870371]
[81]
Tapia, G.; Valenzuela, R.; Espinosa, A.; Romanque, P.; Dossi, C.; Gonzalez-Mañán, D.; Videla, L.A.; D’Espessailles, A. N-3 long-chain PUFA supplementation prevents high fat diet induced mouse liver steatosis and inflammation in relation to PPAR-α upregulation and NF-κB DNA binding abrogation. Mol. Nutr. Food Res., 2014, 58(6), 1333-1341.
[http://dx.doi.org/10.1002/mnfr.201300458] [PMID: 24436018]
[82]
Hernández-Rodas, M.C.; Valenzuela, R.; Echeverría, F.; Rincón-Cervera, M.A.; Espinosa, A.; Illesca, P.; Muñoz, P.; Corbari, A.; Romero, N.; Gonzalez-Mañan, D.; Videla, L.A. Supplementation with docosahexaenoic acid and extra virgin olive oil prevents liver steatosis induced by a high-fat diet in mice through PPAR-α and Nrf2 upregulation with concomitant SREBP-1c and NF-kB downregulation. Mol. Nutr. Food Res., 2017, 61(12) 1700470
[http://dx.doi.org/10.1002/mnfr.201700479] [PMID: 28940752]
[83]
Deng, X.; Dong, Q.; Bridges, D.; Raghow, R.; Park, E.A.; Elam, M.B. Docosahexaenoic acid inhibits proteolytic processing of sterol regulatory element-binding protein-1c (SREBP-1c) via activation of AMP-activated kinase. Biochim. Biophys. Acta, 2015, 1851(12), 1521-1529.
[http://dx.doi.org/10.1016/j.bbalip.2015.08.007] [PMID: 26327595]
[84]
Simopoulos, A.P. Genetic variants in the metabolism of omega-6 and omega-3 fatty acids: their role in the determination of nutritional requirements and chronic disease risk. Exp. Biol. Med. (Maywood), 2010, 235(7), 785-795.
[http://dx.doi.org/10.1258/ebm.2010.009298] [PMID: 20558833]
[85]
Sullivan, E.M.; Pennington, E.R.; Green, W.D.; Beck, M.A.; Brown, D.A.; Shaikh, S.R. Mechanisms by which dietary fatty acids regulate mitochondrial structure-function in health and disease. Adv. Nutr., 2018, 9(3), 247-262.
[http://dx.doi.org/10.1093/advances/nmy007] [PMID: 29767698]
[86]
Wei, Y.; Wang, D.; Topczewski, F.; Pagliassotti, M.J. Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells. Am. J. Physiol. Endocrinol. Metab., 2006, 291(2), E275-E281.
[http://dx.doi.org/10.1152/ajpendo.00644.2005] [PMID: 16492686]
[87]
Zheng, Z.; Zhang, C.; Zhang, K. Role of unfolded protein response in lipogenesis. World J. Hepatol., 2010, 2(6), 203-207.
[http://dx.doi.org/10.4254/wjh.v2.i6.203] [PMID: 21160998]
[88]
Leamy, A.K.; Egnatchik, R.A.; Young, J.D. Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease. Prog. Lipid Res., 2013, 52(1), 165-174.
[http://dx.doi.org/10.1016/j.plipres.2012.10.004] [PMID: 23178552]
[89]
Zhang, Y.; Yang, X.; Shi, H.; Dong, L.; Bai, J. Effect of α-linolenic acid on endoplasmic reticulum stress-mediated apoptosis of palmitic acid lipotoxicity in primary rat hepatocytes. Lipids Health Dis., 2011, 10, 122.
[http://dx.doi.org/10.1186/1476-511X-10-122] [PMID: 21787405]
[90]
Videla, L.A.; Rodrigo, R.; Orellana, M.; Fernández, V.; Tapia, G.; Quiñones, L.; Varela, N.; Contreras, J.; Lazarte, R.; Csendes, A.; Rojas, J.; Maluenda, F.; Burdiles, P.; Diaz, J.C.; Smok, G.; Thielemann, L.; Poniachik, J. Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients. Clin. Sci. (Lond.), 2004, 106(3), 261-268.
[http://dx.doi.org/10.1042/CS20030285] [PMID: 14556645]
[91]
Nakatani, Y.; Kaneto, H.; Kawamori, D.; Yoshiuchi, K.; Hatazaki, M.; Matsuoka, T.A.; Ozawa, K.; Ogawa, S.; Hori, M.; Yamasaki, Y.; Matsuhisa, M. Involvement of endoplasmic reticulum stress in insulin resistance and diabetes. J. Biol. Chem., 2005, 280(1), 847-851.
[http://dx.doi.org/10.1074/jbc.M411860200] [PMID: 15509553]
[92]
Song, J.; Li, C.; Lv, Y.; Zhang, Y.; Amakye, W.K.; Mao, L. DHA increases adiponectin expression more effectively than EPA at relative low concentrations by regulating PPARγ and its phosphorylation at Ser273 in 3T3-L1 adipocytes. Nutr. Metab. (Lond.), 2017, 14, 52.
[http://dx.doi.org/10.1186/s12986-017-0209-z] [PMID: 28811832]
[93]
Miyoshi, H.; Moriya, K.; Tsutsumi, T.; Shinzawa, S.; Fujie, H.; Shintani, Y.; Fujinaga, H.; Goto, K.; Todoroki, T.; Suzuki, T.; Miyamura, T.; Matsuura, Y.; Yotsuyanagi, H.; Koike, K. Pathogenesis of lipid metabolism disorder in hepatitis C: polyunsaturated fatty acids counteract lipid alterations induced by the core protein. J. Hepatol., 2011, 54(3), 432-438.
[http://dx.doi.org/10.1016/j.jhep.2010.07.039] [PMID: 21093950]
[94]
Alwayn, I.P.; Gura, K.; Nosé, V.; Zausche, B.; Javid, P.; Garza, J.; Verbesey, J.; Voss, S.; Ollero, M.; Andersson, C.; Bistrian, B.; Folkman, J.; Puder, M. Omega-3 fatty acid supplementation prevents hepatic steatosis in a murine model of nonalcoholic fatty liver disease. Pediatr. Res., 2005, 57(3), 445-452.
[http://dx.doi.org/10.1203/01.PDR.0000153672.43030.75] [PMID: 15659701]
[95]
González-Périz, A.; Horrillo, R.; Ferré, N.; Gronert, K.; Dong, B.; Morán-Salvador, E.; Titos, E.; Martínez-Clemente, M.; López-Parra, M.; Arroyo, V.; Clària, J. Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. FASEB J., 2009, 23(6), 1946-1957.
[http://dx.doi.org/10.1096/fj.08-125674] [PMID: 19211925]
[96]
Ishii, H.; Horie, Y.; Ohshima, S.; Anezaki, Y.; Kinoshita, N.; Dohmen, T.; Kataoka, E.; Sato, W.; Goto, T.; Sasaki, J.; Sasaki, T.; Watanabe, S.; Suzuki, A.; Ohnishi, H. Eicosapentaenoic acid ameliorates steatohepatitis and hepatocellular carcinoma in hepatocyte-specific Pten-deficient mice. J. Hepatol., 2009, 50(3), 562-571.
[http://dx.doi.org/10.1016/j.jhep.2008.10.031] [PMID: 19162361]
[97]
Svegliati-Baroni, G.; Candelaresi, C.; Saccomanno, S.; Ferretti, G.; Bachetti, T.; Marzioni, M.; De Minicis, S.; Nobili, L.; Salzano, R.; Omenetti, A.; Pacetti, D.; Sigmund, S.; Benedetti, A.; Casini, A. A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptor-alpha and n-3 polyunsaturated fatty acid treatment on liver injury. Am. J. Pathol., 2006, 169(3), 846-860.
[http://dx.doi.org/10.2353/ajpath.2006.050953] [PMID: 16936261]
[98]
Popescu, L.A.; Vîrgolici, B.; Lixandru, D.; Miricescu, D.; Condruţ, E.; Timnea, O.; Ranetti, A.E.; Militaru, M.; Mohora, M.; Zăgrean, L. Effect of diet and omega-3 fatty acids in NAFLD. Rom. J. Morphol. Embryol., 2013, 54(3)(Suppl.), 785-790.
[PMID: 24322028]
[99]
Bargut, T.C.; Frantz, E.D.; Mandarim-de-Lacerda, C.A.; Aguila, M.B. Effects of a diet rich in n-3 polyunsaturated fatty acids on hepatic lipogenesis and beta-oxidation in mice. Lipids, 2014, 49(5), 431-444.
[http://dx.doi.org/10.1007/s11745-014-3892-9] [PMID: 24627299]
[100]
Larter, C.Z.; Yeh, M.M.; Cheng, J.; Williams, J.; Brown, S.; dela Pena, A.; Bell-Anderson, K.S.; Farrell, G.C. Activation of peroxisome proliferator-activated receptor alpha by dietary fish oil attenuates steatosis, but does not prevent experimental steatohepatitis because of hepatic lipoperoxide accumulation. J. Gastroenterol. Hepatol., 2008, 23(2), 267-275.
[http://dx.doi.org/10.1111/j.1440-1746.2007.05157.x] [PMID: 17868330]
[101]
Dossi, C.G.; Tapia, G.S.; Espinosa, A.; Videla, L.A.; D’Espessailles, A. Reversal of high-fat diet-induced hepatic steatosis by n-3 LCPUFA: role of PPAR-α and SREBP-1c. J. Nutr. Biochem., 2014, 25(9), 977-984.
[http://dx.doi.org/10.1016/j.jnutbio.2014.04.011] [PMID: 24993917]
[102]
Louchami, K.; Zhang, Y.; Oguzhan, B.; Delporte, C.; Portois, L.; Carpentier, Y.A.; Genten, F.; Danguy, A.; Malaisse, W.J.; Sener, A. Rapid changes in liver lipid composition and pancreatic islet K+ handling and secretory behaviour provoked by the intravenous administration of a medium-chain triglyceride: fish oil emulsion to long-chain polyunsaturated omega3 fatty acid-depleted rats. Int. J. Mol. Med., 2006, 18(6), 1047-1055.
[http://dx.doi.org/10.3892/ijmm.18.6.1047] [PMID: 17089007]
[103]
Pachikian, B.D.; Neyrinck, A.M.; Cani, P.D.; Portois, L.; Deldicque, L.; De Backer, F.C.; Bindels, L.B.; Sohet, F.M.; Malaisse, W.J.; Francaux, M.; Carpentier, Y.A.; Delzenne, N.M. Hepatic steatosis in n-3 fatty acid depleted mice: focus on metabolic alterations related to tissue fatty acid composition. BMC Physiol., 2008, 8, 21.
[http://dx.doi.org/10.1186/1472-6793-8-21] [PMID: 19046413]
[104]
Kang, J.X.; Wang, J.; Wu, L.; Kang, Z.B. Transgenic mice: fat-1 mice convert n-6 to n-3 fatty acids. Nature, 2004, 427(6974), 504.
[http://dx.doi.org/10.1038/427504a] [PMID: 14765186]
[105]
Kim, E.H.; Bae, J.S.; Hahm, K.B.; Cha, J.Y. Endogenously synthesized n-3 polyunsaturated fatty acids in fat-1 mice ameliorate high-fat diet-induced non-alcoholic fatty liver disease. Biochem. Pharmacol., 2012, 84(10), 1359-1365.
[http://dx.doi.org/10.1016/j.bcp.2012.08.029] [PMID: 22981383]
[106]
Depner, C.M.; Traber, M.G.; Bobe, G.; Kensicki, E.; Bohren, K.M.; Milne, G.; Jump, D.B. A metabolomic analysis of omega-3 fatty acid-mediated attenuation of western diet-induced nonalcoholic steatohepatitis in LDLR-/- mice. PLoS One, 2013, 8(12) e83756
[http://dx.doi.org/10.1371/journal.pone.0083756] [PMID: 24358308]
[107]
López-Vicario, C.; Alcaraz-Quiles, J.; García-Alonso, V.; Rius, B.; Hwang, S.H.; Titos, E.; Lopategi, A.; Hammock, B.D.; Arroyo, V.; Clària, J. Inhibition of soluble epoxide hydrolase modulates inflammation and autophagy in obese adipose tissue and liver: role for omega-3 epoxides. Proc. Natl. Acad. Sci. USA, 2015, 112(2), 536-541.
[http://dx.doi.org/10.1073/pnas.1422590112] [PMID: 25550510]
[108]
Wang, C.; Liu, W.; Yao, L.; Zhang, X.; Zhang, X.; Ye, C.; Jiang, H.; He, J.; Zhu, Y.; Ai, D. Hydroxyeicosapentaenoic acids and epoxyeicosatetraenoic acids attenuate early occurrence of nonalcoholic fatty liver disease. Br. J. Pharmacol., 2017, 174(14), 2358-2372.
[http://dx.doi.org/10.1111/bph.13844] [PMID: 28471490]
[109]
Hanke, D.; Zahradka, P.; Mohankumar, S.K.; Clark, J.L.; Taylor, C.G. A diet high in α-linolenic acid and monounsaturated fatty acids attenuates hepatic steatosis and alters hepatic phospholipid fatty acid profile in diet-induced obese rats. Prostaglandins Leukot. Essent. Fatty Acids, 2013, 89(6), 391-401.
[http://dx.doi.org/10.1016/j.plefa.2013.09.009] [PMID: 24140006]
[110]
Valenzuela, B. R.; Barrera R, C.; González-Astorga, M.; Sanhueza C, J.; Valenzuela B, A. Alpha linolenic acid (ALA) from Rosa canina, sacha inchi and chia oils may increase ALA accretion and its conversion into n-3 LCPUFA in diverse tissues of the rat. Food Funct., 2014, 5(7), 1564-1572.
[http://dx.doi.org/10.1039/C3FO60688K] [PMID: 24855655]
[111]
González-Mañán, D.; D’Espessailles, A.; Dossi, C.G.; San Martín, M.; Mancilla, R.A.; Tapia, G.S. Rosa mosqueta oil prevents oxidative stress and inflammation through the upregulation of PPAR-α and NRF2 in C57BL/6J Mice fed a high-fat diet. J. Nutr., 2017, 147(4), 579-588.
[http://dx.doi.org/10.3945/jn.116.243261] [PMID: 28298541]
[112]
Dossi, C.G.; Cadagan, C.; San Martín, M.; Espinosa, A.; González-Mañán, D.; Silva, D.; Mancilla, R.A.; Tapia, G.S. Effects of Rosa mosqueta oil supplementation in lipogenic markers associated with prevention of liver steatosis. Food Funct., 2017, 8(2), 832-841.
[http://dx.doi.org/10.1039/C6FO01762B] [PMID: 28128380]
[113]
D’Espessailles, A.; Dossi, C.G.; Espinosa, A.; González-Mañán, D.; Tapia, G.S. Dietary Rosa mosqueta (Rosa rubiginosa) oil prevents high diet-induced hepatic steatosis in mice. Food Funct., 2015, 6(9), 3109-3116.
[http://dx.doi.org/10.1039/C5FO00741K] [PMID: 26218006]
[114]
Monteiro, J.; Askarian, F.; Nakamura, M.T.; Moghadasian, M.H.; Ma, D.W. Oils rich in α-linolenic acid independently protect against characteristics of fatty liver disease in the Δ6-desaturase null mouse. Can. J. Physiol. Pharmacol., 2013, 91(6), 469-479.
[http://dx.doi.org/10.1139/cjpp-2012-0308] [PMID: 23746194]
[115]
Kajikawa, S.; Harada, T.; Kawashima, A.; Imada, K.; Mizuguchi, K. Suppression of hepatic fat accumulation by highly purified eicosapentaenoic acid prevents the progression of D-galactosamine-induced hepatitis in mice fed with a high-fat/high-fructose diet. Biochim. Biophys. Acta, 2009, 1791(4), 281-288.
[http://dx.doi.org/10.1016/j.bbalip.2009.01.014]] [PMID: 19416647 ]
[116]
Konuma, K.; Itoh, M.; Suganami, T.; Kanai, S.; Nakagawa, N.; Sakai, T.; Kawano, H.; Hara, M.; Kojima, S.; Izumi, Y.; Ogawa, Y. Eicosapentaenoic acid ameliorates non-alcoholic steatohepatitis in a novel mouse model using melanocortin 4 receptor-deficient mice. PLoS One, 2015, 10(3) e0121528
[http://dx.doi.org/10.1371/journal.pone.0121528] [PMID: 25816330]
[117]
Zhang, K.; Chang, Y.; Shi, Z.; Han, X.; Han, Y.; Yao, Q.; Hu, Z.; Cui, H.; Zheng, L.; Han, T.; Hong, W. ω-3 PUFAs ameliorate liver fibrosis and inhibit hepatic stellate cells proliferation and activation by promoting YAP/TAZ degradation. Sci. Rep., 2016, 6, 30029.
[http://dx.doi.org/10.1038/srep30029] [PMID: 27435808]
[118]
Abo El-Magd, N.F.; El-Karef, A.; El-Shishtawy, M.M.; Eissa, L.A. Hepatoprotective effects of glycyrrhizin and omega-3 fatty acids on nuclear factor-kappa B pathway in thioacetamide-induced fibrosis in rats. Egyptian J. Basic Appl. Sci., 2015, 2, 65-74.
[http://dx.doi.org/10.1016/j.ejbas.2014.12.005]
[119]
Torii, K.; Maeshige, N.; Aoyama-Ishikawa, M.; Miyoshi, M.; Terashi, H.; Usami, M. Combination therapy with butyrate and docosahexaenoic acid for keloid fibrogenesis: an in vitro study. An. Bras. Dermatol., 2017, 92(2), 184-190.
[http://dx.doi.org/10.1590/abd1806-4841.20176198] [PMID: 28538876]
[120]
Li, Y.; Liu, L.; Wang, B.; Xiong, J.; Li, Q.; Wang, J.; Chen, D. Impairment of reproductive function in a male rat model of non-alcoholic fatty liver disease and beneficial effect of N-3 fatty acid supplementation. Toxicol. Lett., 2013, 222(2), 224-232.
[http://dx.doi.org/10.1016/j.toxlet.2013.05.644] [PMID: 23747427]
[121]
Oh, D.Y.; Talukdar, S.; Bae, E.J.; Imamura, T.; Morinaga, H.; Fan, W.; Li, P.; Lu, W.J.; Watkins, S.M.; Olefsky, J.M. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell, 2010, 142(5), 687-698.
[http://dx.doi.org/10.1016/j.cell.2010.07.041] [PMID: 20813258]
[122]
Byrne, C.D.; Olufadi, R.; Bruce, K.D.; Cagampang, F.R.; Ahmed, M.H. Metabolic disturbances in non-alcoholic fatty liver disease. Clin. Sci. (Lond.), 2009, 116(7), 539-564.
[http://dx.doi.org/10.1042/CS20080253] [PMID: 19243311]
[123]
Capanni, M.; Calella, F.; Biagini, M.R.; Genise, S.; Raimondi, L.; Bedogni, G.; Svegliati-Baroni, G.; Sofi, F.; Milani, S.; Abbate, R.; Surrenti, C.; Casini, A. 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(8), 1143-1151.
[http://dx.doi.org/10.1111/j.1365-2036.2006.02885.x] [PMID: 16611275]
[124]
Zhu, F.S.; Liu, S.; Chen, X.M.; Huang, Z.G.; Zhang, D.W. Effects of n-3 polyunsaturated fatty acids from seal oils on nonalcoholic fatty liver disease associated with hyperlipidemia. World J. Gastroenterol., 2008, 14(41), 6395-6400.
[http://dx.doi.org/10.3748/wjg.14.6395] [PMID: 19009658]
[125]
Spadaro, L.; Magliocco, O.; Spampinato, D.; Piro, S.; Oliveri, C.; Alagona, C.; Papa, G.; Rabuazzo, A.M.; Purrello, F. Effects of n-3 polyunsaturated fatty acids in subjects with nonalcoholic fatty liver disease. Dig. Liver Dis., 2008, 40(3), 194-199.
[http://dx.doi.org/10.1016/j.dld.2007.10.003] [PMID: 18054848]
[126]
Sofi, F.; Giangrandi, I.; Cesari, F.; Corsani, I.; Abbate, R.; Gensini, G.F.; Casini, A. Effects of a 1-year dietary intervention with n-3 polyunsaturated fatty acid-enriched olive oil on non-alcoholic fatty liver disease patients: a preliminary study. Int. J. Food Sci. Nutr., 2010, 61(8), 792-802.
[http://dx.doi.org/10.3109/09637486.2010.487480] [PMID: 20465434]
[127]
Oya, J.; Nakagami, T.; Sasaki, S.; Jimba, S.; Murakami, K.; Kasahara, T.; Wasada, T.; Sekiguchi, H.; Hasegawa, M.; Endo, Y.; Iwamoto, Y. Intake of n-3 polyunsaturated fatty acids and non-alcoholic fatty liver disease: a cross-sectional study in Japanese men and women. Eur. J. Clin. Nutr., 2010, 64(10), 1179-1185.
[http://dx.doi.org/10.1038/ejcn.2010.139] [PMID: 20683463]
[128]
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(4), 413-418.
[http://dx.doi.org/10.1097/MCG.0b013e31815591aa] [PMID: 18277895]
[129]
Parker, H.M.; Johnson, N.A.; Burdon, C.A.; Cohn, J.S.; O’Connor, H.T.; George, J. Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J. Hepatol., 2012, 56(4), 944-951.
[http://dx.doi.org/10.1016/j.jhep.2011.08.018] [PMID: 22023985]
[130]
Li, Y.; Chen, D. The optimal dose of omega-3 supplementation for non-alcoholic fatty liver disease. J. Hepatol., 2012, 57(2), 468-469.
[http://dx.doi.org/10.1016/j.jhep.2012.01.028] [PMID: 22433603]
[131]
GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-prevenzione trial. Lancet, 1999, 354(9177), 447-455.
[http://dx.doi.org/10.1016/S0140-6736(99)07072-5] [PMID: 10465168]
[132]
Saravanan, P.; Davidson, N.C.; Schmidt, E.B.; Calder, P.C. Cardiovascular effects of marine omega-3 fatty acids. Lancet, 2010, 376(9740), 540-550.
[http://dx.doi.org/10.1016/S0140-6736(10)60445-X] [PMID: 20638121]
[133]
Petit, J.M.; Guiu, B.; Duvillard, L.; Jooste, V.; Brindisi, M.C.; Athias, A.; Bouillet, B.; Habchi, M.; Cottet, V.; Gambert, P.; Hillon, P.; Cercueil, J.P.; Verges, B. Increased erythrocytes n-3 and n-6 polyunsaturated fatty acids is significantly associated with a lower prevalence of steatosis in patients with type 2 diabetes. Clin. Nutr., 2012, 31(4), 520-525.
[http://dx.doi.org/10.1016/j.clnu.2011.12.007] [PMID: 22209679]
[134]
Scorletti, E.; Bhatia, L.; McCormick, K.G.; Clough, G.F.; Nash, K.; Hodson, L.; Moyses, H.E.; Calder, P.C.; Byrne, C.D. WELCOME Study. Effects of purified eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: results from the welcome* study. Hepatology, 2014, 60(4), 1211-1221.
[http://dx.doi.org/10.1002/hep.27289] [PMID: 25043514]
[135]
Li, Y.H.; Yang, L.H.; Sha, K.H.; Liu, T.G.; Zhang, L.G.; Liu, X.X. Efficacy of poly-unsaturated fatty acid therapy on patients with nonalcoholic steatohepatitis. World J. Gastroenterol., 2015, 21(22), 7008-7013.
[http://dx.doi.org/10.3748/wjg.v21.i22.7008] [PMID: 26078579]
[136]
Nobili, V.; Alisi, A.; Della Corte, C.; Risé, P.; Galli, C.; Agostoni, C.; Bedogni, G. Docosahexaenoic acid for the treatment of fatty liver: randomised controlled trial in children. Nutr. Metab. Cardiovasc. Dis., 2013, 23(11), 1066-1070.
[http://dx.doi.org/10.1016/j.numecd.2012.10.010] [PMID: 23220074]
[137]
Rahmawaty, S.; Lyons-Wall, P.; Charlton, K.; Batterham, M.; Meyer, B.J. Effect of replacing bread, egg, milk, and yogurt with equivalent ω-3 enriched foods on ω-3 LCPUFA intake of Australian children. Nutrition, 2014, 30(11-12), 1337-1343.
[http://dx.doi.org/10.1016/j.nut.2014.03.020] [PMID: 25280409]
[138]
Meyer, B.J.; Kolanu, N. Australian children are not consuming enough long-chain omega-3 polyunsaturated fatty acids for optimal health. Nutrition, 2011, 27(11-12), 1136-1140.
[http://dx.doi.org/10.1016/j.nut.2011.01.004] [PMID: 21658909]
[139]
Janczyk, W.; Lebensztejn, D.; Wierzbicka-Rucińska, A.; Mazur, A.; Neuhoff-Murawska, J.; Matusik, P.; Socha, P. Omega-3 fatty acids therapy in children with nonalcoholic fatty liver disease: a randomized controlled trial. J Pediatr., 2015, 166(6), 1358-1363.e1-3.
[http://dx.doi.org/10.1016/j.jpeds.2015.01.056] [PMID: 25771388]
[140]
Argo, C.K.; Patrie, J.T.; Lackner, C.; Henry, T.D.; de Lange, E.E.; Weltman, A.L.; Shah, N.L.; Al-Osaimi, A.M.; Pramoonjago, P.; Jayakumar, S.; Binder, L.P.; Simmons-Egolf, W.D.; Burks, S.G.; Bao, Y.; Taylor, A.G.; Rodriguez, J.; Caldwell, S.H. Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial. J. Hepatol., 2015, 62(1), 190-197.
[http://dx.doi.org/10.1016/j.jhep.2014.08.036] [PMID: 25195547]
[141]
Dasarathy, S.; Dasarathy, J.; Khiyami, A.; Yerian, L.; Hawkins, C.; Sargent, R.; McCullough, A.J. Double-blind randomized placebo-controlled clinical trial of omega 3 fatty acids for the treatment of diabetic patients with nonalcoholic steatohepatitis. J. Clin. Gastroenterol., 2015, 49(2), 137-144.
[http://dx.doi.org/10.1097/MCG.0000000000000099] [PMID: 24583757]
[142]
Sanyal, A.J.; Abdelmalek, M.F.; Suzuki, A.; Cummings, O.W.; Chojkier, M. EPE-a study group. No significant effects of ethyl-eicosapentanoic acid on histologic features of nonalcoholic steatohepatitis in a phase 2 trial. Gastroenterology, 2014, 147(2), 377-384.e1.
[http://dx.doi.org/10.1053/j.gastro.2014.04.046] [PMID: 24818764]
[143]
Di Minno, M.N.; Russolillo, A.; Lupoli, R.; Ambrosino, P.; Di Minno, A.; Tarantino, G. Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease. World J. Gastroenterol., 2012, 18(41), 5839-5847.
[http://dx.doi.org/10.3748/wjg.v18.i41.5839] [PMID: 23139599]
[144]
Jump, D.B.; Lytle, K.A.; Depner, C.M.; Tripathy, S. Omega-3 polyunsaturated fatty acids as a treatment strategy for nonalcoholic fatty liver disease. Pharmacol. Ther., 2018, 181, 108-125.
[http://dx.doi.org/10.1016/j.pharmthera.2017.07.007] [PMID: 28723414]
[145]
Scorletti, E.; Byrne, C.D. Omega-3 fatty acids and non-alcoholic fatty liver disease: evidence of efficacy and mechanism of action. Mol. Aspects Med., 2018, 64, 135-146.
[http://dx.doi.org/10.1016/j.mam.2018.03.001] [PMID: 29544992 ]
[146]
He, X.X.; Wu, X.L.; Chen, R.P.; Chen, C.; Liu, X.G.; Wu, B.J.; Huang, Z.M. Effectiveness of omega-3 polyunsaturated fatty acids in non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials. PLoS One, 2016, 11(10) e0162368
[http://dx.doi.org/10.1371/journal.pone.0162368] [PMID: 27711128]
[147]
Schuster, S.; Cabrera, D.; Arrese, M.; Feldstein, A.E. Triggering and resolution of inflammation in NASH. Nat. Rev. Gastroenterol. Hepatol., 2018, 15(6), 349-364.
[http://dx.doi.org/10.1038/s41575-018-0009-6] [PMID: 29740166]
[148]
Chen, G.; Xu, R.; Zhang, S.; Wang, Y.; Wang, P.; Edin, M.L.; Zeldin, D.C.; Wang, D.W. CYP2J2 overexpression attenuates nonalcoholic fatty liver disease induced by high-fat diet in mice. Am. J. Physiol. Endocrinol. Metab., 2015, 308(2), E97-E110.
[http://dx.doi.org/10.1152/ajpendo.00366.2014] [PMID: 25389366]
[149]
Schuck, R.N.; Zha, W.; Edin, M.L.; Gruzdev, A.; Vendrov, K.C.; Miller, T.M.; Xu, Z.; Lih, F.B.; DeGraff, L.M.; Tomer, K.B.; Jones, H.M.; Makowski, L.; Huang, L.; Poloyac, S.M.; Zeldin, D.C.; Lee, C.R. The cytochrome P450 epoxygenase pathway regulates the hepatic inflammatory response in fatty liver disease. PLoS One, 2014, 9(10) e110162
[http://dx.doi.org/10.1371/journal.pone.0110162] [PMID: 25310404]
[150]
Valenzuela, R.; Videla, L.A. Crosstalk mechanisms in hepatoprotection: thyroid hormone-docosahexaenoic acid (DHA) and DHA-extra virgin olive oil combined protocols. Pharmacol. Res., 2018, 132, 168-175.
[http://dx.doi.org/10.1016/j.phrs.2017.12.013] [PMID: 29253525]
[151]
Spahis, S.; Delvin, E.; Borys, J.M.; Levy, E. Oxidative stress as a critical factor in nonalcoholic fatty liver disease pathogenesis. Antioxid. Redox Signal., 2017, 26(10), 519-541.
[http://dx.doi.org/10.1089/ars.2016.6776] [PMID: 27452109]
[152]
Masarone, M.; Rosato, V.; Dallio, M.; Gravina, A.G.; Aglitti, A.; Loguercio, C.; Federico, A.; Persico, M. Role of oxidative stress in pathophysiology of nonalcoholic fatty liver disease. Oxid. Med. Cell. Longev., 2018, 2018 9547613
[http://dx.doi.org/10.1155/2018/9547613] [PMID: 29991976]


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VOLUME: 27
ISSUE: 31
Year: 2020
Published on: 10 September, 2020
Page: [5250 - 5272]
Pages: 23
DOI: 10.2174/0929867326666190410121716
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