Abstract
Purpose
The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is still under debate. The aim of this study was to investigate the effects of a long-term fat- and sugar-enriched diet (FSED) and chronic stress (CS) on NAFLD.
Methods
Male Wistar rats were fed on either a standard diet or a FSED and given CS, a random electric foot shock (2 hr/morning and afternoon per day), or not for 12 weeks. After the experimental period, epididymal adipose tissue weight, sign of visceral obesity (VO), and hepatic index (HI) were measured. At sacrifice blood samples and liver were obtained. Histology of the liver was blindly determined by a pathologist.
Results
Histopathologically, moderate to severe steatosis, ballooning hepatocytes, and portal or lobules inflammation were observed in the FSED+CS group. However, mild to moderate steatosis with a few portal inflammation in the FSED group and mild steatosis or not with a few portal inflammation in the CS group were found correspondingly. In addition, more severe blood-fat disorder, high HI, fatty metabolic dysfunction, oxidative stress, high expressions of C-reactive protein mRNA and low expressions of peroxisome proliferator-activated receptor α mRNA in the liver were also revealed in the FSED+CS group. But, the degree of VO was not different between the FSED and FSED+CS groups.
Conclusion
The observations strongly suggest that chronic stress can aggravate fat- and sugar-enriched diet-induced NAFLD from steatosis to steatohepatitis in male Wistar rats, although VO is not changed.
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References
Bellentani S, Tiribelli C, Saccoccio G. Prevalence of chronic liver disease in the general population of northern Italy: The Dionysos study. Hepatology. 1994;20:1442–1449.
Sass DA, Chang P, Chopra KB. Nonalcoholic fatty liver disease: a clinical review. Dig Dis Sci. 2005;50:171–180.
Cave M, Deaciuc I, Mendez C, et al. Nonalcoholic fatty liver disease: predisposing factors and the role of nutrition. J Nutr Biochem. 2007;18:184–195.
Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346:1221–1231.
Harrison SA, Neuschwander-Tetri BA. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Clin Liver Dis. 2004;8:861–879.
McCullough AJ. The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. Clin Liver Dis. 2004;8:521–533.
te Sligte K, Bourass I, Sels JP, Driessenc A, Stockbru Ugger RW, Koek GH. Non-alcoholic steatohepatitis: review of a growing medical problem. Eur J Intern Med. 2004;15:10–21.
Stärkel P, Sempoux C, Leclercq I, et al. Oxidative stress, KLF6 and transforming growth factor-β up-regulation differentiate non-alcoholic steatohepatitis progressing to fibrosis from uncomplicated steatosis in rats. J Hepatol. 2003;39:538–546.
Solga S, Alkhuraishe AR, Clark JM, et al. Dietary composition and nonalcoholic fatty liver disease. Dig Dis Sci. 2004;49:1578–1583.
Elwing JE, Lustman PJ, Wang HL, Ray E. Clouse depression, anxiety, and nonalcoholic steatohepatitis. Psychosom Med. 2006;68:563–569.
Suzuki A, Lindor K, St Saver J, et al. Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease. J Hepatol. 2005;43:1060–1066.
Omagari K, Kato S, Tsuneyama K, et al. 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;53:3206–3212.
Ackerman Z, Oron-Herman M, Rosenthal MGT, Pappo O, Link G, Sela B-A. Fructose-induced fatty liver disease: hepatic effects of blood pressure and plasma triglyceride reduction. Hypertension. 2005;45:1012–1018.
Rosmond R. Role of stress in the pathogenesis of the metabolic syndrome. Psychoneuroendocrinology. 2005;30:1–10.
Koteish A, Diehl AM. Animal models of steatosis. Semin Liver Dis. 2001;21:89–104.
Zou YH, Li J, Lu C, et al. High-fat emulsion-induced rat model of nonalcoholic steatohepatitis. Life Sci. 2006;79:1100–1107.
Lieber CS, Leo MA, Mak KM, et al. Model of nonalcoholic steatohepatitis. Am J Clin Nutr. 2004;79:502–509.
Fu JH, Xie SR, Kong SJ, et al. The combination of a high-fat diet and chronic stress aggravates insulin resistance in Wistar male rats. Exp Clin Endocrinol Diabetes. 2009;117(7):354–360.
Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–1321.
Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116:1413–1419.
Day CP, James OF. Steatohepatitis: A tale of two “hits”? Gastroenterology. 1998;114(4):842–845.
McClain CJ, Mokshagundam SPL, Barve SS, et al. Mechanisms of non-alcoholic steatohepatitis. Alcohol. 2004;34:67–79.
Havel PJ, Uriu-Hare JY, Liu T, et al. Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats: reversal by insulin. Am J Physiol. 1998;274:R1482–R1491.
Rybkin II, Zhou Y, Volaufova J, Smagin GN, Ryan DH, Harris RB. Effect of restraint stress on food intake and body weight is determined by time of day. Am J Physiol. 1997;273:1612–1622.
Harris RBS, Zhou J, Youngblood BD, Rybkin II, Smagin GN, Ryan DH. Effect of repeated stress on body weight and body composition of rats fed low-and high-fat diets. Am J Physiol Regul Integr Comp Physiol. 1998;275:1928–1938.
Black PH. The inflammatory response is an integral part of the stress response: implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X. Brain Behav Immun. 2003;17:350–364.
Agrawal A, Cha-Molstad H, Samols D, Kushner I. Transactivation of C-reactive protein by IL-6 requires synergistic interaction of CCAAT/enhancer binding protein beta (C/EBP beta) and Rel p50. J Immunol. 2001;166(4):2378–2384.
Lemberger T, Saladin R, Va zquez Manuel, et al. Expression of the peroxisome proliferator-activated receptor a gene is stimulated by stress and follows a diurnal rhythm. J Biol Chem. 1996;271:1764–1769.
Guan Y. Targeting peroxisome proliferator activated receptors (PPARs) in kidney and urologic disease. Minerva Urol Nefrol. 2002;54:65–79.
Guan Y, Breyer MD. Peroxisome proliferator activated receptors (PPARs): novel therapeutic targets in renal disease. Kidney Int. 2001;60:14–30.
Ip E, Farrell GC, Field J, et al. Central role of PPARα-dependent hepatic lipid turnover in dietary steatohepatitis in mice. Hepatology. 2003;38:123–132.
Kawanaka M, Mahmood S, Niiyama G, et al. Control of oxidative stress and reduction in biochemical markers by vitamin E treatment in patients with nonalcoholic steatohepatitis: a pilot study. Hepatol Res. 2004;29:39–41.
Videla LA. Oxidative stress and depletion of hepatic long-chain polyunsatureted fatty acids may contribute to nonalcoholic fatty liver disease. Free Radic Biol Med. 2004;37(9):1499–1507.
Kahn R. Metabolic syndrome is it a syndrome? Does it matter? Circulation. 2007;115:1806–1811.
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Fu, Jh., Sun, Hs., Wang, Y. et al. The Effects of a Fat- and Sugar-Enriched Diet and Chronic Stress on Nonalcoholic Fatty Liver Disease in Male Wistar Rats. Dig Dis Sci 55, 2227–2236 (2010). https://doi.org/10.1007/s10620-009-1019-6
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DOI: https://doi.org/10.1007/s10620-009-1019-6