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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Review Article

Fatty Acids and Effects on In Vitro and In Vivo Models of Liver Steatosis

Author(s): Laura Vergani*

Volume 26, Issue 19, 2019

Page: [3439 - 3456] Pages: 18

DOI: 10.2174/0929867324666170518101334

Price: $65

Abstract

Background: Fatty liver, or steatosis, is a condition of excess accumulation of lipids, mainly under form of triglycerides (TG), in the liver, and it is the hallmark of non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common liver disorder world-wide and it has frequently been associated with obesity, hyperlipidemia and insulin resistance. Free fatty acids (FA) are the major mediators of hepatic steatosis; patients with NAFLD have elevated levels of circulating FA that correlate with disease severity.

Methods: Steatosis is a reversible condition that can be resolved with changed behaviors, or that can progress towards more severe liver damages such as steatohepatitis (NASH), fibrosis and cirrhosis. In NAFLD, FA of exogenous or endogenous origin accumulate in the hepatocytes and trigger liver damages. Excess TG are stored in cytosolic lipid droplets (LDs) that are dynamic organelles acting as hubs for lipid metabolism.

Results: In the first part of this review, we briefly reassumed the main classes of FA and their chemical classification as a function of the presence and number of double bonds, their metabolic pathways and effects on human health. Then, we summarized the main genetic and diet-induced animal models of NAFLD, as well as the cellular models of NAFLD.

Conclusions: In recent years, both the diet-induced animal models of NAFLD as well as the cellular models of NAFLD have found ever more application to investigate the mechanisms involved in NAFLD, and we referred to their advantages and disadvantages.

Keywords: Fatty acids, hepatic steatosis, Nonalcoholic Fatty Liver Disease (NAFLD), Reactive Oxygen Species (ROS), fatty acid oxidation, lipid metabolism, oxidative stress, Lipid Droplets (LDs).

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[1]
Rinella, M.E. Nonalcoholic fatty liver disease: a systematic review. JAMA, 2015, 313(22), 2263-2273.
[http://dx.doi.org/10.1001/jama.2015.5370] [PMID: 26057287]
[2]
Bradbury, M.W.; Berk, P.D. Lipid metabolism in hepatic steatosis. Clin. Liver Dis., 2004, 8(3), 639-671. xi. [xi]
[http://dx.doi.org/10.1016/j.cld.2004.04.005] [PMID: 15331068]
[3]
Brunt, E.M.; Wong, V.W.S.; Nobili, V.; Day, C.P.; Sookoian, S.; Maher, J.J.; Bugianesi, E.; Sirlin, C.B.; Neuschwander-Tetri, B.A.; Rinella, M.E. Nonalcoholic fatty liver disease. Nat. Rev. Dis. Prim, 2004, 8(3), 639-671. xi.2015
[4]
Tilg, H.; Moschen, A.R. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology, 2010, 52(5), 1836-1846.
[http://dx.doi.org/10.1002/hep.24001] [PMID: 21038418]
[5]
Nehra, V.; Angulo, P.; Buchman, A.L.; Lindor, K.D. Nutritional and metabolic considerations in the etiology of nonalcoholic steatohepatitis. Dig. Dis. Sci., 2001, 46(11), 2347-2352.
[http://dx.doi.org/10.1023/A:1012338828418] [PMID: 11713934]
[6]
Pohl, J.; Ring, A.; Ehehalt, R.; Herrmann, T.; Stremmel, W. New concepts of cellular fatty acid uptake: role of fatty acid transport proteins and of caveolae. Proc. Nutr. Soc., 2004, 63(2), 259-262.
[http://dx.doi.org/10.1079/PNS2004341] [PMID: 15294040]
[7]
Ehehalt, R.; Füllekrug, J.; Pohl, J.; Ring, A.; Herrmann, T.; Stremmel, W. Translocation of long chain fatty acids across the plasma membrane--lipid rafts and fatty acid transport proteins. Mol. Cell. Biochem., 2006, 284(1-2), 135-140.
[http://dx.doi.org/10.1007/s11010-005-9034-1] [PMID: 16477381]
[8]
Stremmel, W.; Pohl, L.; Ring, A.; Herrmann, T. A new concept of cellular uptake and intracellular trafficking of long-chain fatty acids. Lipids, 2001, 36(9), 981-989.
[http://dx.doi.org/10.1007/s11745-001-0809-2] [PMID: 11724471]
[9]
Musso, G.; Gambino, R.; Cassader, M. Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD). Prog. Lipid Res., 2009, 48(1), 1-26.
[http://dx.doi.org/10.1016/j.plipres.2008.08.001] [PMID: 18824034]
[10]
Fernández-Rojo, M.A.; Restall, C.; Ferguson, C.; Martel, N.; Martin, S.; Bosch, M.; Kassan, A.; Leong, G.M.; Martin, S.D.; McGee, S.L.; Muscat, G.E.; Anderson, R.L.; Enrich, C.; Pol, A.; Parton, R.G. Caveolin-1 orchestrates the balance between glucose and lipid-dependent energy metabolism: implications for liver regeneration. Hepatology, 2012, 55(5), 1574-1584.
[http://dx.doi.org/10.1002/hep.24810] [PMID: 22105343]
[11]
Hubbard, B.; Doege, H.; Punreddy, S.; Wu, H.; Huang, X.; Kaushik, V.K.; Mozell, R.L.; Byrnes, J.J.; Stricker-Krongrad, A.; Chou, C.J.; Tartaglia, L.A.; Lodish, H.F.; Stahl, A.; Gimeno, R.E. Mice deleted for fatty acid transport protein 5 have defective bile acid conjugation and are protected from obesity. Gastroenterology, 2006, 130(4), 1259-1269.
[http://dx.doi.org/10.1053/j.gastro.2006.02.012] [PMID: 16618417]
[12]
Koonen, D.P.; Jacobs, R.L.; Febbraio, M.; Young, M.E.; Soltys, C.L.; Ong, H.; Vance, D.E.; Dyck, J.R. Increased hepatic CD36 expression contributes to dyslipidemia associated with diet-induced obesity. Diabetes, 2007, 56(12), 2863-2871.
[http://dx.doi.org/10.2337/db07-0907] [PMID: 17728375]
[13]
Zhou, J.; Febbraio, M.; Wada, T.; Zhai, Y.; Kuruba, R.; He, J.; Lee, J.H.; Khadem, S.; Ren, S.; Li, S.; Silverstein, R.L.; Xie, W. Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR, and PPARgamma in promoting steatosis. Gastroenterology, 2008, 134(2), 556-567.
[http://dx.doi.org/10.1053/j.gastro.2007.11.037] [PMID: 18242221]
[14]
Makowski, L.; Hotamisligil, G.S. The role of fatty acid binding proteins in metabolic syndrome and atherosclerosis. Curr. Opin. Lipidol., 2005, 16(5), 543-548.
[http://dx.doi.org/10.1097/01.mol.0000180166.08196.07] [PMID: 16148539]
[15]
Donnelly, K.L.; Smith, C.I.; Schwarzenberg, S.J.; Jessurun, J.; Boldt, M.D.; Parks, E.J. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J. Clin. Invest., 2005, 115(5), 1343-1351.
[http://dx.doi.org/10.1172/JCI23621] [PMID: 15864352]
[16]
Thiele, C.; Spandl, J. Cell biology of lipid droplets. Curr. Opin. Cell Biol., 2008, 20(4), 378-385.
[http://dx.doi.org/10.1016/j.ceb.2008.05.009] [PMID: 18606534]
[17]
Reddy, J.K. Nonalcoholic steatosis and steatohepatitis. III. Peroxisomal beta-oxidation, PPAR alpha, and steatohepatitis. Am. J. Physiol. Gastrointest. Liver Physiol., 2001, 281(6), G1333-G1339.
[http://dx.doi.org/10.1152/ajpgi.2001.281.6.G1333] [PMID: 11705737]
[18]
Macdonald, G.A.; Prins, J.B. Peroxisomal fatty acid metabolism, peroxisomal proliferator-activated receptors and non-alcoholic fatty liver disease. J. Gastroenterol. Hepatol., 2004, 19(12), 1335-1337.
[http://dx.doi.org/10.1111/j.1440-1746.2004.03562.x] [PMID: 15610304]
[19]
Mannaerts, G.P.; Van Veldhoven, P.P.; Casteels, M. Peroxisomal lipid degradation via beta- and alpha-oxidation in mammals. Cell Biochem. Biophys., 2000, 32(Spring), 73-87.
[http://dx.doi.org/10.1385/CBB:32:1-3:73] [PMID: 11330072]
[20]
Hua, X.; Wu, J.; Goldstein, J.L.; Brown, M.S.; Hobbs, H.H. Structure of the human gene encoding sterol regulatory element binding protein-1 (SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17p11.2 and 22q13. Genomics, 1995, 25(3), 667-673.
[http://dx.doi.org/10.1016/0888-7543(95)80009-B] [PMID: 7759101]
[21]
Azzout-Marniche, D.; Bécard, D.; Guichard, C.; Foretz, M.; Ferré, P.; Foufelle, F. Insulin effects on sterol regulatory-element-binding protein-1c (SREBP-1c) transcriptional activity in rat hepatocytes. Biochem. J., 2000, 350(Pt 2), 389-393.
[http://dx.doi.org/10.1042/bj3500389] [PMID: 10947952]
[22]
Foretz, M.; Pacot, C.; Dugail, I.; Lemarchand, P.; Guichard, C.; Le Lièpvre, X.; Berthelier-Lubrano, C.; Spiegelman, B.; Kim, J.B.; Ferré, P.; Foufelle, F. ADD1/SREBP-1c is required in the activation of hepatic lipogenic gene expression by glucose. Mol. Cell. Biol., 1999, 19(5), 3760-3768.
[http://dx.doi.org/10.1128/MCB.19.5.3760] [PMID: 10207099]
[23]
Kohjima, M.; Higuchi, N.; Kato, M.; Kotoh, K.; Yoshimoto, T.; Fujino, T.; Yada, M.; Yada, R.; Harada, N.; Enjoji, M.; Takayanagi, R.; Nakamuta, M. SREBP-1c, regulated by the insulin and AMPK signaling pathways, plays a role in nonalcoholic fatty liver disease. Int. J. Mol. Med., 2008, 21(4), 507-511.
[http://dx.doi.org/10.3892/ijmm.21.4.507] [PMID: 18360697]
[24]
Shimomura, I.; Bashmakov, Y.; Horton, J.D. Increased levels of nuclear SREBP-1c associated with fatty livers in two mouse models of diabetes mellitus. J. Biol. Chem., 1999, 274(42), 30028-30032.
[http://dx.doi.org/10.1074/jbc.274.42.30028] [PMID: 10514488]
[25]
Horton, J.D.; Bashmakov, Y.; Shimomura, I.; Shimano, H. Regulation of sterol regulatory element binding proteins in livers of fasted and refed mice. Proc. Natl. Acad. Sci. USA, 1998, 95(11), 5987-5992.
[http://dx.doi.org/10.1073/pnas.95.11.5987] [PMID: 9600904]
[26]
Wang, D.; Wei, Y.; Pagliassotti, M.J. Saturated fatty acids promote endoplasmic reticulum stress and liver injury in rats with hepatic steatosis. Endocrinology, 2006, 147(2), 943-951.
[http://dx.doi.org/10.1210/en.2005-0570] [PMID: 16269465]
[27]
Poulsen, Ll.; Siersbæk, M.; Mandrup, S. PPARs: fatty acid sensors controlling metabolism. Semin. Cell Dev. Biol., 2012, 23(6), 631-639.
[http://dx.doi.org/10.1016/j.semcdb.2012.01.003] [PMID: 22273692]
[28]
Escher, P.; Braissant, O.; Basu-Modak, S.; Michalik, L.; Wahli, W.; Desvergne, B. Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting and refeeding. Endocrinology, 2001, 142(10), 4195-4202.
[http://dx.doi.org/10.1210/endo.142.10.8458] [PMID: 11564675]
[29]
Varga, T.; Czimmerer, Z.; Nagy, L. PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation. Biochim. Biophys. Acta, 2011, 1812(8), 1007-1022.
[http://dx.doi.org/10.1016/j.bbadis.2011.02.014] [PMID: 21382489]
[30]
Calder, P.C. Polyunsaturated fatty acids, inflammatory processes and inflammatory bowel diseases. Mol. Nutr. Food Res., 2008, 52(8), 885-897.
[http://dx.doi.org/10.1002/mnfr.200700289] [PMID: 18504706]
[31]
Simopoulos, A.P. Evolutionary aspects of diet: the omega-6/omega-3 ratio and the brain. Mol. Neurobiol., 2011, 44(2), 203-215.
[http://dx.doi.org/10.1007/s12035-010-8162-0] [PMID: 21279554]
[32]
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]
[33]
Tsantila, N.; Karantonis, H.C.; Perrea, D.N.; Theocharis, S.E.; Iliopoulos, D.G.; Antonopoulou, S.; Demopoulos, C.A. Antithrombotic and antiatherosclerotic properties of olive oil and olive pomace polar extracts in rabbits. Mediators Inflamm., 2007, 2007, 36204.
[http://dx.doi.org/10.1155/2007/36204] [PMID: 18253466]
[34]
Tvrzicka, E.; Vecka, M.; Stankova, B.; Zak, A. Analysis of fatty acids in plasma lipoproteins by gas chromatography-flame ionization detection: Quantitative aspects. Anal. Chim. Acta, 2002, 465, 337-350.
[http://dx.doi.org/10.1016/S0003-2670(02)00396-3]
[35]
Kitaura, Y.; Inoue, K.; Kato, N.; Matsushita, N.; Shimomura, Y. Enhanced oleate uptake and lipotoxicity associated with laurate. FEBS Open Bio, 2015, 5, 485-491.
[http://dx.doi.org/10.1016/j.fob.2015.05.008] [PMID: 26106523]
[36]
Mensink, R.P.; Katan, M.B. Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials. Arterioscler. Thromb., 1992, 12(8), 911-919.
[http://dx.doi.org/10.1161/01.ATV.12.8.911] [PMID: 1386252]
[37]
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]
[38]
El-Badry, A.M.; Graf, R.; Clavien, P.A. Omega 3 - Omega 6: what is right for the liver? J. Hepatol., 2007, 47(5), 718-725.
[http://dx.doi.org/10.1016/j.jhep.2007.08.005] [PMID: 17869370]
[39]
Kolakowska, A.; Kolakowski, E.; Szczygielski, M. Winter season krill (Euphausia superba Dana) as a source of n-3 polyunsaturated fatty acids. Food/Nahrung, 2007, 38, 128-134. 1994
[40]
Ferramosca, A.; Conte, A.; Burri, L.; Berge, K.; De Nuccio, F.; Giudetti, A.M.; Zara, V. A krill oil supplemented diet suppresses hepatic steatosis in high-fat fed rats. PLoS One, 2012, 7(6)e38797
[http://dx.doi.org/10.1371/journal.pone.0038797] [PMID: 22685607]
[41]
Bunea, R.; El Farrah, K.; Deutsch, L. Evaluation of the effects of Neptune Krill Oil on the clinical course of hyperlipidemia. Altern. Med. Rev., 2004, 9(4), 420-428.
[PMID: 15656713]
[42]
Summers, L.K.; Fielding, B.A.; Bradshaw, H.A.; Ilic, V.; Beysen, C.; Clark, M.L.; Moore, N.R.; Frayn, K.N. Substituting dietary saturated fat with polyunsaturated fat changes abdominal fat distribution and improves insulin sensitivity. Diabetologia, 2002, 45(3), 369-377.
[http://dx.doi.org/10.1007/s00125-001-0768-3] [PMID: 11914742]
[43]
Mozaffarian, D.; Micha, R.; Wallace, S. Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. PLoS Med., 2010, 7(3)e1000252
[http://dx.doi.org/10.1371/journal.pmed.1000252] [PMID: 20351774]
[44]
Astrup, A.; Dyerberg, J.; Elwood, P.; Hermansen, K.; Hu, F.B.; Jakobsen, M.U.; Kok, F.J.; Krauss, R.M.; Lecerf, J.M.; LeGrand, P.; Nestel, P.; Risérus, U.; Sanders, T.; Sinclair, A.; Stender, S.; Tholstrup, T.; Willett, W.C. The role of reducing intakes of saturated fat in the prevention of cardiovascular disease: where does the evidence stand in 2010? Am. J. Clin. Nutr., 2011, 93(4), 684-688.
[http://dx.doi.org/10.3945/ajcn.110.004622] [PMID: 21270379]
[45]
Risérus, U.; Willett, W.C.; Hu, F.B. Dietary fats and prevention of type 2 diabetes. Prog. Lipid Res., 2009, 48(1), 44-51.
[http://dx.doi.org/10.1016/j.plipres.2008.10.002] [PMID: 19032965]
[46]
Jump, D.B. Fatty acid regulation of hepatic lipid metabolism. Curr. Opin. Clin. Nutr. Metab. Care, 2011, 14(2), 115-120.
[http://dx.doi.org/10.1097/MCO.0b013e328342991c] [PMID: 21178610]
[47]
Sekiya, M.; Yahagi, N.; Matsuzaka, T.; Najima, Y.; Nakakuki, M.; Nagai, R.; Ishibashi, S.; Osuga, J.; Yamada, N.; Shimano, H. Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Hepatology, 2003, 38(6), 1529-1539.
[http://dx.doi.org/10.1053/jhep.2003.09028] [PMID: 14647064]
[48]
Schmitz, G.; Ecker, J. The opposing effects of n-3 and n-6 fatty acids. Prog. Lipid Res., 2008, 47(2), 147-155.
[http://dx.doi.org/10.1016/j.plipres.2007.12.004] [PMID: 18198131]
[49]
Molendi-Coste, O.; Legry, V.; Leclercq, I.A. Why and how meet n-3 PUFA dietary recommendations? Gastroenterol. Res. Pract., 2011.2011364040
[http://dx.doi.org/10.1155/2011/364040] [PMID: 21197079]
[50]
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]
[51]
Santoro, N.; Caprio, S.; Giannini, C.; Kim, G.; Kursawe, R.; Pierpont, B.; Shaw, M.M.; Feldstein, A.E. Oxidized fatty acids: A potential pathogenic link between fatty liver and type 2 diabetes in obese adolescents? Antioxid. Redox Signal., 2014, 20(2), 383-389.
[http://dx.doi.org/10.1089/ars.2013.5466] [PMID: 23815500]
[52]
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]
[53]
Abifadel, M.; Varret, M.; Rabès, J.P.; Allard, D.; Ouguerram, K.; Devillers, M.; Cruaud, C.; Benjannet, S.; Wickham, L.; Erlich, D.; Derré, A.; Villéger, L.; Farnier, M.; Beucler, I.; Bruckert, E.; Chambaz, J.; Chanu, B.; Lecerf, J.M.; Luc, G.; Moulin, P.; Weissenbach, J.; Prat, A.; Krempf, M.; Junien, C.; Seidah, N.G.; Boileau, C. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat. Genet., 2003, 34(2), 154-156.
[http://dx.doi.org/10.1038/ng1161] [PMID: 12730697]
[54]
Morimoto, M.; Zern, M.A.; Hagbjörk, A.L.; Ingelman-Sundberg, M.; French, S.W. Fish oil, alcohol, and liver pathology: role of cytochrome P450 2E1. Proc. Soc. Exp. Biol. Med., 1994, 207(2), 197-205.
[http://dx.doi.org/10.3181/00379727-207-43807] [PMID: 7938050]
[55]
Nanji, A.A. Role of different dietary fatty acids in the pathogenesis of experimental alcoholic liver disease. Alcohol, 2004, 34(1), 21-25.
[http://dx.doi.org/10.1016/j.alcohol.2004.08.005] [PMID: 15670661]
[56]
Mayer, J.; Bates, M.W.; Dickie, M.M. Hereditary diabetes in genetically obese mice. Science, 1951, 113(2948), 746-747.
[http://dx.doi.org/10.1126/science.113.2948.746] [PMID: 14854871]
[57]
Brix, A.E.; Elgavish, A.; Nagy, T.R.; Gower, B.A.; Rhead, W.J.; Wood, P.A. Evaluation of liver fatty acid oxidation in the leptin-deficient obese mouse. Mol. Genet. Metab., 2002, 75(3), 219-226.
[http://dx.doi.org/10.1006/mgme.2002.3298] [PMID: 11914033]
[58]
Wortham, M.; He, L.; Gyamfi, M.; Copple, B.L.; Wan, Y.J. The transition from fatty liver to NASH associates with SAMe depletion in db/db mice fed a methionine choline-deficient diet. Dig. Dis. Sci., 2008, 53(10), 2761-2774.
[http://dx.doi.org/10.1007/s10620-007-0193-7] [PMID: 18299981]
[59]
Godbole, V.; York, D.A. Lipogenesis in situ in the genetically obese Zucker fatty rat (fa/fa): role of hyperphagia and hyperinsulinaemia. Diabetologia, 1978, 14(3), 191-197.
[http://dx.doi.org/10.1007/BF00429780] [PMID: 566233]
[60]
Masaki, T.; Chiba, S.; Tatsukawa, H.; Yasuda, T.; Noguchi, H.; Seike, M.; Yoshimatsu, H. Adiponectin protects LPS-induced liver injury through modulation of TNF-alpha in KK-Ay obese mice. Hepatology, 2004, 40(1), 177-184.
[http://dx.doi.org/10.1002/hep.20282] [PMID: 15239101]
[61]
Nakayama, H.; Otabe, S.; Ueno, T.; Hirota, N.; Yuan, X.; Fukutani, T.; Hashinaga, T.; Wada, N.; Yamada, K. Transgenic mice expressing nuclear sterol regulatory element-binding protein 1c in adipose tissue exhibit liver histology similar to nonalcoholic steatohepatitis. Metabolism, 2007, 56(4), 470-475.
[http://dx.doi.org/10.1016/j.metabol.2006.11.004] [PMID: 17379003]
[62]
Li, J.; Yen, C.; Liaw, D.; Podsypanina, K.; Bose, S.; Wang, S.I.; Puc, J.; Miliaresis, C.; Rodgers, L.; McCombie, R.; Bigner, S.H.; Giovanella, B.C.; Ittmann, M.; Tycko, B.; Hibshoosh, H.; Wigler, M.H.; Parsons, R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 1997, 275(5308), 1943-1947.
[http://dx.doi.org/10.1126/science.275.5308.1943] [PMID: 9072974]
[63]
Horie, Y.; Suzuki, A.; Kataoka, E.; Sasaki, T.; Hamada, K.; Sasaki, J.; Mizuno, K.; Hasegawa, G.; Kishimoto, H.; Iizuka, M.; Naito, M.; Enomoto, K.; Watanabe, S.; Mak, T.W.; Nakano, T. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J. Clin. Invest., 2004, 113(12), 1774-1783.
[http://dx.doi.org/10.1172/JCI20513] [PMID: 15199412]
[64]
Balthasar, N.; Dalgaard, L.T.; Lee, C.E.; Yu, J.; Funahashi, H.; Williams, T.; Ferreira, M.; Tang, V.; McGovern, R.A.; Kenny, C.D.; Christiansen, L.M.; Edelstein, E.; Choi, B.; Boss, O.; Aschkenasi, C.; Zhang, C.Y.; Mountjoy, K.; Kishi, T.; Elmquist, J.K.; Lowell, B.B. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell, 2005, 123(3), 493-505.
[http://dx.doi.org/10.1016/j.cell.2005.08.035] [PMID: 16269339]
[65]
Albarado, D.C.; McClaine, J.; Stephens, J.M.; Mynatt, R.L.; Ye, J.; Bannon, A.W.; Richards, W.G.; Butler, A.A. Impaired coordination of nutrient intake and substrate oxidation in melanocortin-4 receptor knockout mice. Endocrinology, 2004, 145(1), 243-252.
[http://dx.doi.org/10.1210/en.2003-0452] [PMID: 14551222]
[66]
Rinella, M.E.; Green, R.M. The methionine-choline deficient dietary model of steatohepatitis does not exhibit insulin resistance. J. Hepatol., 2004, 40(1), 47-51.
[http://dx.doi.org/10.1016/j.jhep.2003.09.020] [PMID: 14672613]
[67]
Anstee, Q.M.; Goldin, R.D. Mouse models in non-alcoholic fatty liver disease and steatohepatitis research. Int. J. Exp. Pathol., 2006, 87(1), 1-16.
[http://dx.doi.org/10.1111/j.0959-9673.2006.00465.x] [PMID: 16436109]
[68]
Grasselli, E.; Canesi, L.; Voci, A.; De Matteis, R.; Demori, I.; Fugassa, E.; Vergani, L. Effects of 3,5-diiodo-L-thyronine administration on the liver of high fat diet-fed rats. Exp. Biol. Med. (Maywood), 2008, 233(5), 549-557.
[http://dx.doi.org/10.3181/0710-RM-266] [PMID: 18375830]
[69]
Bray, G.A.; Paeratakul, S.; Popkin, B.M. Dietary fat and obesity: a review of animal, clinical and epidemiological studies. Physiol. Behav., 2004, 83(4), 549-555.
[http://dx.doi.org/10.1016/j.physbeh.2004.08.039] [PMID: 15621059]
[70]
Omagari, K.; Kato, S.; Tsuneyama, K.; Inohara, C.; Kuroda, Y.; Tsukuda, H.; Fukazawa, E.; Shiraishi, K.; Mune, M. Effects of a long-term high-fat diet and switching from a high-fat to low-fat, standard diet on hepatic fat accumulation in Sprague-Dawley rats. Dig. Dis. Sci., 2008, 53(12), 3206-3212.
[http://dx.doi.org/10.1007/s10620-008-0303-1] [PMID: 18465233]
[71]
Varela-Rey, M.; Embade, N.; Ariz, U.; Lu, S.C.; Mato, J.M.; Martínez-Chantar, M.L. Non-alcoholic steatohepatitis and animal models: understanding the human disease. Int. J. Biochem. Cell Biol., 2009, 41(5), 969-976.
[http://dx.doi.org/10.1016/j.biocel.2008.10.027] [PMID: 19027869]
[72]
Cong, W.N.; Tao, R.Y.; Tian, J.Y.; Liu, G.T.; Ye, F. The establishment of a novel non-alcoholic steatohepatitis model accompanied with obesity and insulin resistance in mice. Life Sci., 2008, 82(19-20), 983-990.
[http://dx.doi.org/10.1016/j.lfs.2008.01.022] [PMID: 18417155]
[73]
Deng, Q.G.; She, H.; Cheng, J.H.; French, S.W.; Koop, D.R.; Xiong, S.; Tsukamoto, H. Steatohepatitis induced by intragastric overfeeding in mice. Hepatology, 2005, 42(4), 905-914.
[http://dx.doi.org/10.1002/hep.20877] [PMID: 16175602]
[74]
Li, Z.; Soloski, M.J.; Diehl, A.M. Dietary factors alter hepatic innate immune system in mice with nonalcoholic fatty liver disease. Hepatology, 2005, 42(4), 880-885.
[http://dx.doi.org/10.1002/hep.20826] [PMID: 16175608]
[75]
Tipoe, G.L.; Ho, C.T.; Liong, E.C.; Leung, T.M.; Lau, T.Y.; Fung, M.L.; Nanji, A.A. Voluntary oral feeding of rats not requiring a very high fat diet is a clinically relevant animal model of non-alcoholic fatty liver disease (NAFLD). Histol. Histopathol., 2009, 24(9), 1161-1169. [NAFLD]
[PMID: 19609863]
[76]
Nishina, P.M.; Verstuyft, J.; Paigen, B. Synthetic low and high fat diets for the study of atherosclerosis in the mouse. J. Lipid Res., 1990, 31(5), 859-869.
[PMID: 2380634]
[77]
Kumar, S.A.; Sudhahar, V.; Varalakshmi, P. Protective role of eicosapentaenoate-lipoate (EPA-LA) derivative in combating oxidative hepatocellular injury in hypercholesterolemic atherogenesis. Atherosclerosis, 2006, 189(1), 115-122.
[http://dx.doi.org/10.1016/j.atherosclerosis.2005.11.037] [PMID: 16458314]
[78]
Shockley, K.R.; Witmer, D.; Burgess-Herbert, S.L.; Paigen, B.; Churchill, G.A. Effects of atherogenic diet on hepatic gene expression across mouse strains. Physiol. Genomics, 2009, 39(3), 172-182.
[http://dx.doi.org/10.1152/physiolgenomics.90350.2008] [PMID: 19671657]
[79]
Matsuzawa, N.; Takamura, T.; Kurita, S.; Misu, H.; Ota, T.; Ando, H.; Yokoyama, M.; Honda, M.; Zen, Y.; Nakanuma, Y.; Miyamoto, K.; Kaneko, S. Lipid-induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet. Hepatology, 2007, 46(5), 1392-1403.
[http://dx.doi.org/10.1002/hep.21874] [PMID: 17929294]
[80]
Spruss, A.; Bergheim, I. Dietary fructose and intestinal barrier: potential risk factor in the pathogenesis of nonalcoholic fatty liver disease. J. Nutr. Biochem., 2009, 20(9), 657-662.
[http://dx.doi.org/10.1016/j.jnutbio.2009.05.006] [PMID: 19679262]
[81]
Tappy, L.; Lê, K.A.; Tran, C.; Paquot, N. Fructose and metabolic diseases: new findings, new questions. Nutrition, 2010, 26(11-12), 1044-1049.
[http://dx.doi.org/10.1016/j.nut.2010.02.014] [PMID: 20471804]
[82]
Bergheim, I.; Weber, S.; Vos, M.; Krämer, S.; Volynets, V.; Kaserouni, S.; McClain, C.J.; Bischoff, S.C. Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin. J. Hepatol., 2008, 48(6), 983-992.
[http://dx.doi.org/10.1016/j.jhep.2008.01.035] [PMID: 18395289]
[83]
Charlton, M.; Krishnan, A.; Viker, K.; Sanderson, S.; Cazanave, S.; McConico, A.; Masuoko, H.; Gores, G. Fast food diet mouse: novel small animal model of NASH with ballooning, progressive fibrosis, and high physiological fidelity to the human condition. Am. J. Physiol. Gastrointest. Liver Physiol., 2011, 301(5), G825-G834.
[http://dx.doi.org/10.1152/ajpgi.00145.2011] [PMID: 21836057]
[84]
Chavez-Tapia, N.C.; Rosso, N.; Tiribelli, C. In vitro models for the study of non-alcoholic fatty liver disease. Curr. Med. Chem., 2011, 18(7), 1079-1084.
[http://dx.doi.org/10.2174/092986711794940842] [PMID: 21254970]
[85]
Malhi, H.; Bronk, S.F.; Werneburg, N.W.; Gores, G.J. Free fatty acids induce JNK-dependent hepatocyte lipoapoptosis. J. Biol. Chem., 2006, 281(17), 12093-12101.
[http://dx.doi.org/10.1074/jbc.M510660200] [PMID: 16505490]
[86]
Gómez-Lechón, M.J.; Donato, M.T.; Martínez-Romero, A.; Jiménez, N.; Castell, J.V.; O’Connor, J.E. A human hepatocellular in vitro model to investigate steatosis. Chem. Biol. Interact., 2007, 165(2), 106-116.
[http://dx.doi.org/10.1016/j.cbi.2006.11.004] [PMID: 17188672]
[87]
Ricchi, M.; Odoardi, M.R.; Carulli, L.; Anzivino, C.; Ballestri, S.; Pinetti, A.; Fantoni, L.I.; Marra, F.; Bertolotti, M.; Banni, S.; Lonardo, A.; Carulli, N.; Loria, P. Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes. J. Gastroenterol. Hepatol., 2009, 24(5), 830-840.
[http://dx.doi.org/10.1111/j.1440-1746.2008.05733.x] [PMID: 19207680]
[88]
Okamoto, Y.; Tanaka, S.; Haga, Y. Enhanced GLUT2 gene expression in an oleic acid-induced in vitro fatty liver model. Hepatol. Res., 2002, 23(2), 138-144.
[http://dx.doi.org/10.1016/S1386-6346(01)00172-3] [PMID: 12048068]
[89]
Cui, W.; Chen, S.L.; Hu, K.Q. Quantification and mechanisms of oleic acid-induced steatosis in HepG2 cells. Am. J. Transl. Res., 2010, 2(1), 95-104.
[PMID: 20182586]
[90]
AlGhamdi, S.; Leoncikas, V.; Plant, K.E.; Plant, N.J. Synergistic interaction between lipid-loading and doxorubicin exposure in Huh7 hepatoma cells results in enhanced cytotoxicity and cellular oxidative stress: implications for acute and chronic care of obese cancer patients. Toxicol. Res. (Camb.), 2015, 4(6), 1479-1487.
[http://dx.doi.org/10.1039/C5TX00173K] [PMID: 26744621]
[91]
De Gottardi, A.; Vinciguerra, M.; Sgroi, A.; Moukil, M.; Ravier-Dall’Antonia, F.; Pazienza, V.; Pugnale, P.; Foti, M.; Hadengue, A. Microarray analyses and molecular profiling of steatosis induction in immortalized human hepatocytes. Lab. Invest., 2007, 87(8), 792-806.
[http://dx.doi.org/10.1038/labinvest.3700590] [PMID: 17558421]
[92]
Grasselli, E.; Voci, A.; Canesi, L.; Goglia, F.; Ravera, S.; Panfoli, I.; Gallo, G.; Vergani, L. Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells. J. Endocrinol., 2011, 210(1), 59-69.
[http://dx.doi.org/10.1530/JOE-11-0074] [PMID: 21508094]
[93]
Grasselli, E.; Voci, A.; Canesi, L.; Salis, A.; Damonte, G.; Compalati, A.D.; Goglia, F.; Gallo, G.; Vergani, L. 3,5-diiodo-L-thyronine modifies the lipid droplet composition in a model of hepatosteatosis. Cell. Physiol. Biochem., 2014, 33(2), 344-356.
[http://dx.doi.org/10.1159/000356674] [PMID: 24525903]
[94]
Grasselli, E.; Voci, A.; Pesce, C.; Canesi, L.; Fugassa, E.; Gallo, G.; Vergani, L. PAT protein mRNA expression in primary rat hepatocytes: Effects of exposure to fatty acids. Int. J. Mol. Med., 2010, 25(4), 505-512.
[PMID: 20198297]
[95]
Grasselli, E.; Voci, A.; Canesi, L.; De Matteis, R.; Goglia, F.; Cioffi, F.; Fugassa, E.; Gallo, G.; Vergani, L. Direct effects of iodothyronines on excess fat storage in rat hepatocytes. J. Hepatol., 2011, 54(6), 1230-1236.
[http://dx.doi.org/10.1016/j.jhep.2010.09.027] [PMID: 21145833]
[96]
Wobser, H.; Dorn, C.; Weiss, T.S.; Amann, T.; Bollheimer, C.; Büttner, R.; Schölmerich, J.; Hellerbrand, C. Lipid accumulation in hepatocytes induces fibrogenic activation of hepatic stellate cells. Cell Res., 2009, 19(8), 996-1005.
[http://dx.doi.org/10.1038/cr.2009.73] [PMID: 19546889]

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