Experimental models of non-alcoholic fatty liver disease in rats
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
25024595
PubMed Central
PMC4093690
DOI
10.3748/wjg.v20.i26.8364
Knihovny.cz E-zdroje
- Klíčová slova
- Animal model, High-fat diet, Methionine- and choline-deficient diet, Non-alcoholic fatty liver disease, Non-alcoholic steatohepatitis, Otsuka-Long-Evans-Tokushima fatty rats, Zucker rats,
- MeSH
- druhová specificita MeSH
- fenotyp MeSH
- genetická predispozice k nemoci MeSH
- jaterní cirhóza metabolismus patologie patofyziologie MeSH
- játra metabolismus patologie patofyziologie MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- modely nemocí na zvířatech * MeSH
- nealkoholová steatóza jater * etiologie genetika metabolismus patologie patofyziologie MeSH
- nutriční stav MeSH
- progrese nemoci MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, and it persists at a high prevalence. NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings, ranging from simple fatty liver through non-alcoholic steatohepatitis (NASH) to fibrosis and ultimately cirrhosis, which may progress to hepatocellular carcinoma. The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance. Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models. The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages. Within the past several years, great emphasis has been placed on the development of an appropriate model for human NASH. This paper reviews the widely used experimental models of NAFLD in rats. We discuss nutritional, genetic and combined models of NAFLD and their pros and cons. The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies. Considering the legislative, ethical, economical and health factors of NAFLD, animal models are essential tools for the research of this disease.
Zobrazit více v PubMed
Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34:274–285. PubMed
Yki-Järvinen H. Nutritional modulation of nonalcoholic fatty liver disease and insulin resistance: human data. Curr Opin Clin Nutr Metab Care. 2010;13:709–714. PubMed
Anstee QM, Day CP. The genetics of NAFLD. Nat Rev Gastroenterol Hepatol. 2013;10:645–655. PubMed
Ekstedt M, Franzén LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, Kechagias S. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006;44:865–873. PubMed
Tessari P, Coracina A, Cosma A, Tiengo A. Hepatic lipid metabolism and non-alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis. 2009;19:291–302. PubMed
Charlton M, Sreekumar R, Rasmussen D, Lindor K, Nair KS. Apolipoprotein synthesis in nonalcoholic steatohepatitis. Hepatology. 2002;35:898–904. PubMed
Samuel VT, Liu ZX, Qu X, Elder BD, Bilz S, Befroy D, Romanelli AJ, Shulman GI. Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem. 2004;279:32345–32353. PubMed
Ferré P, Foufelle F. SREBP-1c transcription factor and lipid homeostasis: clinical perspective. Horm Res. 2007;68:72–82. PubMed
Valenti L, Fracanzani AL, Dongiovanni P, Santorelli G, Branchi A, Taioli E, Fiorelli G, Fargion S. Tumor necrosis factor alpha promoter polymorphisms and insulin resistance in nonalcoholic fatty liver disease. Gastroenterology. 2002;122:274–280. PubMed
Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology. 1998;114:842–845. PubMed
Marra F, Gastaldelli A, Svegliati Baroni G, Tell G, Tiribelli C. Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis. Trends Mol Med. 2008;14:72–81. PubMed
Wieckowska A, Zein NN, Yerian LM, Lopez AR, McCullough AJ, Feldstein AE. In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease. Hepatology. 2006;44:27–33. PubMed
Jou J, Choi SS, Diehl AM. Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liver Dis. 2008;28:370–379. PubMed
Larter CZ, Yeh MM. Animal models of NASH: getting both pathology and metabolic context right. J Gastroenterol Hepatol. 2008;23:1635–1648. PubMed
Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–1321. PubMed
Kleiner DE, Brunt EM. Nonalcoholic fatty liver disease: pathologic patterns and biopsy evaluation in clinical research. Semin Liver Dis. 2012;32:3–13. PubMed
Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55:2005–2023. PubMed
Ribeiro PS, Cortez-Pinto H, Solá S, Castro RE, Ramalho RM, Baptista A, Moura MC, Camilo ME, Rodrigues CM. Hepatocyte apoptosis, expression of death receptors, and activation of NF-kappaB in the liver of nonalcoholic and alcoholic steatohepatitis patients. Am J Gastroenterol. 2004;99:1708–1717. PubMed
Wieckowska A, Feldstein AE. Diagnosis of nonalcoholic fatty liver disease: invasive versus noninvasive. Semin Liver Dis. 2008;28:386–395. PubMed
Schattenberg JM, Galle PR. Animal models of non-alcoholic steatohepatitis: of mice and man. Dig Dis. 2010;28:247–254. PubMed
London RM, George J. Pathogenesis of NASH: animal models. Clin Liver Dis. 2007;11:55–74, viii. PubMed
Fellmann L, Nascimento AR, Tibiriça E, Bousquet P. Murine models for pharmacological studies of the metabolic syndrome. Pharmacol Ther. 2013;137:331–340. PubMed
Kučera O, Garnol T, Lotková H, Staňková P, Mazurová Y, Hroch M, Bolehovská R, Roušar T, Červinková Z. The effect of rat strain, diet composition and feeding period on the development of a nutritional model of non-alcoholic fatty liver disease in rats. Physiol Res. 2011;60:317–328. PubMed
Rosenstengel S, Stoeppeler S, Bahde R, Spiegel HU, Palmes D. Type of steatosis influences microcirculation and fibrogenesis in different rat strains. J Invest Surg. 2011;24:273–282. PubMed
Stöppeler S, Palmes D, Fehr M, Hölzen JP, Zibert A, Siaj R, Schmidt HH, Spiegel HU, Bahde R. Gender and strain-specific differences in the development of steatosis in rats. Lab Anim. 2013;47:43–52. PubMed
Romestaing C, Piquet MA, Bedu E, Rouleau V, Dautresme M, Hourmand-Ollivier I, Filippi C, Duchamp C, Sibille B. Long term highly saturated fat diet does not induce NASH in Wistar rats. Nutr Metab (Lond) 2007;4:4. PubMed PMC
Zou Y, Li J, Lu C, Wang J, Ge J, Huang Y, Zhang L, Wang Y. High-fat emulsion-induced rat model of nonalcoholic steatohepatitis. Life Sci. 2006;79:1100–1107. PubMed
Baumgardner JN, Shankar K, Hennings L, Badger TM, Ronis MJ. A new model for nonalcoholic steatohepatitis in the rat utilizing total enteral nutrition to overfeed a high-polyunsaturated fat diet. Am J Physiol Gastrointest Liver Physiol. 2008;294:G27–G38. PubMed
Lieber CS, Leo MA, Mak KM, Xu Y, Cao Q, Ren C, Ponomarenko A, DeCarli LM. Model of nonalcoholic steatohepatitis. Am J Clin Nutr. 2004;79:502–509. PubMed
Jump DB, Tripathy S, Depner CM. Fatty acid-regulated transcription factors in the liver. Annu Rev Nutr. 2013;33:249–269. PubMed PMC
Tschöp M, Heiman ML. Rodent obesity models: an overview. Exp Clin Endocrinol Diabetes. 2001;109:307–319. PubMed
Takahashi Y, Soejima Y, Fukusato T. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2012;18:2300–2308. PubMed PMC
Hamaguchi M, Kojima T, Ohbora A, Takeda N, Fukui M, Kato T. Aging is a risk factor of nonalcoholic fatty liver disease in premenopausal women. World J Gastroenterol. 2012;18:237–243. PubMed PMC
Svegliati-Baroni G, Candelaresi C, Saccomanno S, Ferretti G, Bachetti T, Marzioni M, De Minicis S, Nobili L, Salzano R, Omenetti A, et al. 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;169:846–860. PubMed PMC
Buettner R, Parhofer KG, Woenckhaus M, Wrede CE, Kunz-Schughart LA, Schölmerich J, Bollheimer LC. Defining high-fat-diet rat models: metabolic and molecular effects of different fat types. J Mol Endocrinol. 2006;36:485–501. PubMed
Ahmed U, Redgrave TG, Oates PS. Effect of dietary fat to produce non-alcoholic fatty liver in the rat. J Gastroenterol Hepatol. 2009;24:1463–1471. PubMed
Wang Y, Ausman LM, Russell RM, Greenberg AS, Wang XD. Increased apoptosis in high-fat diet-induced nonalcoholic steatohepatitis in rats is associated with c-Jun NH2-terminal kinase activation and elevated proapoptotic Bax. J Nutr. 2008;138:1866–1871. PubMed PMC
Li Y, Hai J, Li L, Chen X, Peng H, Cao M, Zhang Q. Administration of ghrelin improves inflammation, oxidative stress, and apoptosis during and after non-alcoholic fatty liver disease development. Endocrine. 2013;43:376–386. PubMed
Simopoulos AP. Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomed Pharmacother. 2006;60:502–507. PubMed
Wouters K, van Gorp PJ, Bieghs V, Gijbels MJ, Duimel H, Lütjohann D, Kerksiek A, van Kruchten R, Maeda N, Staels B, et al. Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis. Hepatology. 2008;48:474–486. PubMed
Wang W, Zhao C, Zhou J, Zhen Z, Wang Y, Shen C. Simvastatin ameliorates liver fibrosis via mediating nitric oxide synthase in rats with non-alcoholic steatohepatitis-related liver fibrosis. PLoS One. 2013;8:e76538. PubMed PMC
Xu ZJ, Fan JG, Ding XD, Qiao L, Wang GL. Characterization of high-fat, diet-induced, non-alcoholic steatohepatitis with fibrosis in rats. Dig Dis Sci. 2010;55:931–940. PubMed PMC
Zhang W, Wang LW, Wang LK, Li X, Zhang H, Luo LP, Song JC, Gong ZJ. Betaine protects against high-fat-diet-induced liver injury by inhibition of high-mobility group box 1 and Toll-like receptor 4 expression in rats. Dig Dis Sci. 2013;58:3198–3206. PubMed
Lim JS, Mietus-Snyder M, Valente A, Schwarz JM, Lustig RH. The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome. Nat Rev Gastroenterol Hepatol. 2010;7:251–264. PubMed
Armutcu F, Coskun O, Gürel A, Kanter M, Can M, Ucar F, Unalacak M. Thymosin alpha 1 attenuates lipid peroxidation and improves fructose-induced steatohepatitis in rats. Clin Biochem. 2005;38:540–547. PubMed
Kawasaki T, Igarashi K, Koeda T, Sugimoto K, Nakagawa K, Hayashi S, Yamaji R, Inui H, Fukusato T, Yamanouchi T. Rats fed fructose-enriched diets have characteristics of nonalcoholic hepatic steatosis. J Nutr. 2009;139:2067–2071. PubMed
Tian YF, He CT, Chen YT, Hsieh PS. Lipoic acid suppresses portal endotoxemia-induced steatohepatitis and pancreatic inflammation in rats. World J Gastroenterol. 2013;19:2761–2771. PubMed PMC
Panchal SK, Poudyal H, Iyer A, Nazer R, Alam MA, Diwan V, Kauter K, Sernia C, Campbell F, Ward L, et al. High-carbohydrate, high-fat diet-induced metabolic syndrome and cardiovascular remodeling in rats. J Cardiovasc Pharmacol. 2011;57:611–624. PubMed
Sampey BP, Vanhoose AM, Winfield HM, Freemerman AJ, Muehlbauer MJ, Fueger PT, Newgard CB, Makowski L. Cafeteria diet is a robust model of human metabolic syndrome with liver and adipose inflammation: comparison to high-fat diet. Obesity (Silver Spring) 2011;19:1109–1117. PubMed PMC
Lombardi B, Pani P, Schlunk FF. Choline-deficiency fatty liver: impaired release of hepatic triglycerides. J Lipid Res. 1968;9:437–446. PubMed
Ghoshal AK. New insight into the biochemical pathology of liver in choline deficiency. Crit Rev Biochem Mol Biol. 1995;30:263–273. PubMed
Veteläinen R, van Vliet A, van Gulik TM. Essential pathogenic and metabolic differences in steatosis induced by choline or methione-choline deficient diets in a rat model. J Gastroenterol Hepatol. 2007;22:1526–1533. PubMed
Al-Humadi H, Theocharis S, Dontas I, Stolakis V, Zarros A, Kyriakaki A, Al-Saigh R, Liapi C. Hepatic injury due to combined choline-deprivation and thioacetamide administration: an experimental approach to liver diseases. Dig Dis Sci. 2012;57:3168–3177. PubMed
Tahan V, Eren F, Avsar E, Yavuz D, Yuksel M, Emekli E, Imeryuz N, Celikel C, Uzun H, Haklar G, et al. Rosiglitazone attenuates liver inflammation in a rat model of nonalcoholic steatohepatitis. Dig Dis Sci. 2007;52:3465–3472. PubMed
Ota T, Takamura T, Kurita S, Matsuzawa N, Kita Y, Uno M, Akahori H, Misu H, Sakurai M, Zen Y, et al. Insulin resistance accelerates a dietary rat model of nonalcoholic steatohepatitis. Gastroenterology. 2007;132:282–293. PubMed
Serviddio G, Bellanti F, Giudetti AM, Gnoni GV, Petrella A, Tamborra R, Romano AD, Rollo T, Vendemiale G, Altomare E. A silybin-phospholipid complex prevents mitochondrial dysfunction in a rodent model of nonalcoholic steatohepatitis. J Pharmacol Exp Ther. 2010;332:922–932. PubMed
Zhang BH, Weltman M, Farrell GC. Does steatohepatitis impair liver regeneration? A study in a dietary model of non-alcoholic steatohepatitis in rats. J Gastroenterol Hepatol. 1999;14:133–137. PubMed
Romestaing C, Piquet MA, Letexier D, Rey B, Mourier A, Servais S, Belouze M, Rouleau V, Dautresme M, Ollivier I, et al. Mitochondrial adaptations to steatohepatitis induced by a methionine- and choline-deficient diet. Am J Physiol Endocrinol Metab. 2008;294:E110–E119. PubMed
Serviddio G, Bellanti F, Tamborra R, Rollo T, Capitanio N, Romano AD, Sastre J, Vendemiale G, Altomare E. Uncoupling protein-2 (UCP2) induces mitochondrial proton leak and increases susceptibility of non-alcoholic steatohepatitis (NASH) liver to ischaemia-reperfusion injury. Gut. 2008;57:957–965. PubMed
Stärkel P, Sempoux C, Leclercq I, Herin M, Deby C, Desager JP, Horsmans Y. Oxidative stress, KLF6 and transforming growth factor-beta up-regulation differentiate non-alcoholic steatohepatitis progressing to fibrosis from uncomplicated steatosis in rats. J Hepatol. 2003;39:538–546. PubMed
Kirsch R, Clarkson V, Shephard EG, Marais DA, Jaffer MA, Woodburne VE, Kirsch RE, Hall Pde L. Rodent nutritional model of non-alcoholic steatohepatitis: species, strain and sex difference studies. J Gastroenterol Hepatol. 2003;18:1272–1282. PubMed
Kawaratani H, Tsujimoto T, Kitazawa T, Kitade M, Yoshiji H, Uemura M, Fukui H. Innate immune reactivity of the liver in rats fed a choline-deficient L-amino-acid-defined diet. World J Gastroenterol. 2008;14:6655–6661. PubMed PMC
Nakae D, Mizumoto Y, Andoh N, Tamura K, Horiguchi K, Endoh T, Kobayashi E, Tsujiuchi T, Denda A, Lombardi B. Comparative changes in the liver of female Fischer-344 rats after short-term feeding of a semipurified or a semisynthetic L-amino acid-defined choline-deficient diet. Toxicol Pathol. 1995;23:583–590. PubMed
Uto H, Nakanishi C, Ido A, Hasuike S, Kusumoto K, Abe H, Numata M, Nagata K, Hayashi K, Tsubouchi H. The peroxisome proliferator-activated receptor-gamma agonist, pioglitazone, inhibits fat accumulation and fibrosis in the livers of rats fed a choline-deficient, l-amino acid-defined diet. Hepatol Res. 2005;32:235–242. PubMed
Larter CZ. Not all models of fatty liver are created equal: understanding mechanisms of steatosis development is important. J Gastroenterol Hepatol. 2007;22:1353–1354. PubMed
Vendemiale G, Grattagliano I, Caraceni P, Caraccio G, Domenicali M, Dall’Agata M, Trevisani F, Guerrieri F, Bernardi M, Altomare E. Mitochondrial oxidative injury and energy metabolism alteration in rat fatty liver: effect of the nutritional status. Hepatology. 2001;33:808–815. PubMed
Hensley K, Kotake Y, Sang H, Pye QN, Wallis GL, Kolker LM, Tabatabaie T, Stewart CA, Konishi Y, Nakae D, et al. Dietary choline restriction causes complex I dysfunction and increased H(2)O(2) generation in liver mitochondria. Carcinogenesis. 2000;21:983–989. PubMed
Nagarajan P, Mahesh Kumar MJ, Venkatesan R, Majundar SS, Juyal RC. Genetically modified mouse models for the study of nonalcoholic fatty liver disease. World J Gastroenterol. 2012;18:1141–1153. PubMed PMC
Yamashita T, Murakami T, Iida M, Kuwajima M, Shima K. Leptin receptor of Zucker fatty rat performs reduced signal transduction. Diabetes. 1997;46:1077–1080. PubMed
Ahima RS, Flier JS. Leptin. Annu Rev Physiol. 2000;62:413–437. PubMed
Qamar A, Sheikh SZ, Masud A, Jhandier MN, Inayat IB, Hakim W, Mehal WZ. In vitro and in vivo protection of stellate cells from apoptosis by leptin. Dig Dis Sci. 2006;51:1697–1705. PubMed PMC
Godbole V, York DA. Lipogenesis in situ in the genetically obese Zucker fatty rat (fa/fa): role of hyperphagia and hyperinsulinaemia. Diabetologia. 1978;14:191–197. PubMed
Oana F, Takeda H, Hayakawa K, Matsuzawa A, Akahane S, Isaji M, Akahane M. Physiological difference between obese (fa/fa) Zucker rats and lean Zucker rats concerning adiponectin. Metabolism. 2005;54:995–1001. PubMed
Liao W, Angelin B, Rudling M. Lipoprotein metabolism in the fat Zucker rat: reduced basal expression but normal regulation of hepatic low density lipoprotein receptors. Endocrinology. 1997;138:3276–3282. PubMed
Witztum JL, Schonfeld G. Lipoproteins in the plasma and hepatic perfusates of the Zucker fatty rat. Diabetes. 1979;28:509–516. PubMed
Kurtz TW, Morris RC, Pershadsingh HA. The Zucker fatty rat as a genetic model of obesity and hypertension. Hypertension. 1989;13:896–901. PubMed
Yang SQ, Lin HZ, Lane MD, Clemens M, Diehl AM. Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci USA. 1997;94:2557–2562. PubMed PMC
Carmiel-Haggai M, Cederbaum AI, Nieto N. A high-fat diet leads to the progression of non-alcoholic fatty liver disease in obese rats. FASEB J. 2005;19:136–138. PubMed
Soltys K, Dikdan G, Koneru B. Oxidative stress in fatty livers of obese Zucker rats: rapid amelioration and improved tolerance to warm ischemia with tocopherol. Hepatology. 2001;34:13–18. PubMed
Selzner M, Clavien PA. Failure of regeneration of the steatotic rat liver: disruption at two different levels in the regeneration pathway. Hepatology. 2000;31:35–42. PubMed
Kakuma T, Lee Y, Higa M, Wang Zw, Pan W, Shimomura I, Unger RH. Leptin, troglitazone, and the expression of sterol regulatory element binding proteins in liver and pancreatic islets. Proc Natl Acad Sci USA. 2000;97:8536–8541. PubMed PMC
Letexier D, Peroni O, Pinteur C, Beylot M. In vivo expression of carbohydrate responsive element binding protein in lean and obese rats. Diabetes Metab. 2005;31:558–566. PubMed
Fukunishi S, Nishio H, Fukuda A, Takeshita A, Hanafusa T, Higuchi K, Suzuki K. Development of Fibrosis in Nonalcoholic Steatosis through Combination of a Synthetic Diet Rich in Disaccharide and Low-Dose Lipopolysaccharides in the Livers of Zucker (fa/fa) Rats. J Clin Biochem Nutr. 2009;45:322–328. PubMed PMC
Yang YY, Tsai TH, Huang YT, Lee TY, Chan CC, Lee KC, Lin HC. Hepatic endothelin-1 and endocannabinoids-dependent effects of hyperleptinemia in nonalcoholic steatohepatitis-cirrhotic rats. Hepatology. 2012;55:1540–1550. PubMed
Clark JB, Palmer CJ, Shaw WN. The diabetic Zucker fatty rat. Proc Soc Exp Biol Med. 1983;173:68–75. PubMed
Etgen GJ, Oldham BA. Profiling of Zucker diabetic fatty rats in their progression to the overt diabetic state. Metabolism. 2000;49:684–688. PubMed
Corsetti JP, Sparks JD, Peterson RG, Smith RL, Sparks CE. Effect of dietary fat on the development of non-insulin dependent diabetes mellitus in obese Zucker diabetic fatty male and female rats. Atherosclerosis. 2000;148:231–241. PubMed
Chalasani N, Crabb DW, Cummings OW, Kwo PY, Asghar A, Pandya PK, Considine RV. Does leptin play a role in the pathogenesis of human nonalcoholic steatohepatitis? Am J Gastroenterol. 2003;98:2771–2776. PubMed
Takaya K, Ogawa Y, Hiraoka J, Hosoda K, Yamori Y, Nakao K, Koletsky RJ. Nonsense mutation of leptin receptor in the obese spontaneously hypertensive Koletsky rat. Nat Genet. 1996;14:130–131. PubMed
Koletsky S. Pathologic findings and laboratory data in a new strain of obese hypertensive rats. Am J Pathol. 1975;80:129–142. PubMed PMC
Elam MB, Wilcox HG, Cagen LM, Deng X, Raghow R, Kumar P, Heimberg M, Russell JC. Increased hepatic VLDL secretion, lipogenesis, and SREBP-1 expression in the corpulent JCR: LA-cp rat. J Lipid Res. 2001;42:2039–2048. PubMed
Wexler BC. Hyperlipidemia, hyperglycemia and hypertension in repeatedly bred parents of the obese spontaneously hypertensive rat (obese/SHR) unaccompanied by arteriosclerosis. Atherosclerosis. 1984;51:211–222. PubMed
Kitamori K, Naito H, Tamada H, Kobayashi M, Miyazawa D, Yasui Y, Sonoda K, Tsuchikura S, Yasui N, Ikeda K, et al. Development of novel rat model for high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr. Environ Health Prev Med. 2012;17:173–182. PubMed PMC
Qi NR, Wang J, Zidek V, Landa V, Mlejnek P, Kazdová L, Pravenec M, Kurtz TW. A new transgenic rat model of hepatic steatosis and the metabolic syndrome. Hypertension. 2005;45:1004–1011. PubMed
Eberlé D, Clément K, Meyre D, Sahbatou M, Vaxillaire M, Le Gall A, Ferré P, Basdevant A, Froguel P, Foufelle F. SREBF-1 gene polymorphisms are associated with obesity and type 2 diabetes in French obese and diabetic cohorts. Diabetes. 2004;53:2153–2157. PubMed
Malínská H, Oliyarnyk O, Hubová M, Zídek V, Landa V, Simáková M, Mlejnek P, Kazdová L, Kurtz TW, Pravenec M. Increased liver oxidative stress and altered PUFA metabolism precede development of non-alcoholic steatohepatitis in SREBP-1a transgenic spontaneously hypertensive rats with genetic predisposition to hepatic steatosis. Mol Cell Biochem. 2010;335:119–125. PubMed
Takiguchi S, Takata Y, Funakoshi A, Miyasaka K, Kataoka K, Fujimura Y, Goto T, Kono A. Disrupted cholecystokinin type-A receptor (CCKAR) gene in OLETF rats. Gene. 1997;197:169–175. PubMed
Jung TS, Kim SK, Shin HJ, Jeon BT, Hahm JR, Roh GS. α-lipoic acid prevents non-alcoholic fatty liver disease in OLETF rats. Liver Int. 2012;32:1565–1573. PubMed
Kawano K, Hirashima T, Mori S, Saitoh Y, Kurosumi M, Natori T. Spontaneous long-term hyperglycemic rat with diabetic complications. Otsuka Long-Evans Tokushima Fatty (OLETF) strain. Diabetes. 1992;41:1422–1428. PubMed
Song YS, Fang CH, So BI, Park JY, Lee Y, Shin JH, Jun DW, Kim H, Kim KS. Time course of the development of nonalcoholic Fatty liver disease in the Otsuka long-evans Tokushima Fatty rat. Gastroenterol Res Pract. 2013;2013:342648. PubMed PMC
Yeon JE, Choi KM, Baik SH, Kim KO, Lim HJ, Park KH, Kim JY, Park JJ, Kim JS, Bak YT, et al. Reduced expression of peroxisome proliferator-activated receptor-alpha may have an important role in the development of non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2004;19:799–804. PubMed
Uno M, Kurita S, Misu H, Ando H, Ota T, Matsuzawa-Nagata N, Kita Y, Nabemoto S, Akahori H, Zen Y, et al. Tranilast, an antifibrogenic agent, ameliorates a dietary rat model of nonalcoholic steatohepatitis. Hepatology. 2008;48:109–118. PubMed
Kovár J, Tonar Z, Heczková M, Poledne R. Prague hereditary hypercholesterolemic (PHHC) rat - a model of polygenic hypercholesterolemia. Physiol Res. 2009;58 Suppl 2:S95–S99. PubMed