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Taurine attenuates the development of hepatic steatosis through the inhibition of oxidative stress in a model of nonalcoholic fatty liver disease in vivo and in vitro

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Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. It is characterized by the accumulation of triglyceride within hepatocytes. Taurine is a sulfur-containing-β-amino acid that is widely distributed in mammalian tissues. The objective of this study was to examine the effects of taurine on the development of hepatic steatosis in a model of NAFLD in vivo and in vitro. Male C57BL/6J mice were fed a high-fat diet (HFD) supplemented with 2% (w/v) or 5% (w/v) taurine for 12 weeks. An in vitro study was performed in HepG2 cells loaded with fatty acids. Twelve weeks of supplementation with an HFD increased the hepatic lipid levels and oxidative stress as well as the body weight and liver weight. Taurine significantly suppressed these changes, which was accompanied by a decrease in the hepatic level of thiobarbituric acid-reactive substances (TBARS). In addition, taurine treatment suppressed the HFD-induced reduction of the enzyme activity of hepatic superoxide dismutase and catalase and the reduction of the hepatic level of reduced glutathione and ATP. In HepG2 cells, taurine suppressed the fatty acid-induced lipid accumulation, production of reactive oxygen species and TBARS level, and amelioration of the fatty acid-induced disruption of the mitochondrial membrane potential. These results showed that taurine was effective in alleviating hepatic steatosis by reducing oxidative stress. Taurine may, therefore, be of therapeutic value in reducing the risks associated with NAFLD.

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Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

CAT:

Catalase

GSH:

Reduced glutathione

HDL:

High-density lipoprotein

HFD:

High-fat diet

NAFLD:

Nonalcoholic fatty liver disease

ROS:

Reactive oxygen species

PBS:

Phosphate-buffered saline

SOD:

Superoxide dismutase

TBARS:

Thiobarbituric acid-reactive substances

VLDL:

Very low-density lipoprotein

References

  • Abenavoli L, Peta V (2014) Role of adipokines and cytokines in non-alcoholic fatty liver disease. Rev Recent Clin Trials 9:134–140

    Article  PubMed  CAS  Google Scholar 

  • Aruoma OI, Halliwell B, Hoey BM, Butler J (1998) The antioxidant action of taurine, hypotaurine and their metabolic precursors. Biochem J 256:251–255

    Article  Google Scholar 

  • Bonfleur ML, Borck PC, Ribeiro RA, Caetano LC, Soares GM, Carneiro EM, Balbo SL (2015) Improvement in the expression of hepatic genes involved in fatty acid metabolism in obese rats supplemented with taurine. Life Sci 135:15–21

    Article  PubMed  CAS  Google Scholar 

  • Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH (2004) Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40:1387–1395

    Article  PubMed  Google Scholar 

  • Brunt E (2010) Pathology of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 7:195–203

    Article  PubMed  Google Scholar 

  • Chen SW, Chen YX, Shi J, Lin Y, Xie WF (2006) The restorative effect of taurine on experimental nonalcoholic steatohepatitis. Dig Dis Sci 51:2225–2234

    Article  PubMed  CAS  Google Scholar 

  • Das J, Ghosh J, Manna P, Sil PC (2010) Protective role of taurine against arsenic-induced mitochondria-dependent hepatic apoptosis via the inhibition of PKCdelta–JNK pathway. PLoS One 5:e12602

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dietrich P, Hellerbrand C (2014) Non-alcoholic fatty liver disease, obesity and the metabolic syndrome. Best Pract Res Clin Gastroenterol 28:637–653

    Article  PubMed  CAS  Google Scholar 

  • Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ (2005) Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Investig 115:1343–1351

    Article  PubMed  CAS  Google Scholar 

  • Fukuda N, Yoshitama A, Sugita S, Fujita M, Murakami S (2011) Dietary taurine reduces hepatic secretion of cholesteryl ester and enhances fatty acid oxidation in rats fed a high-cholesterol diet. J Nutr Sci Vitaminol 57:144–1449

    Article  PubMed  CAS  Google Scholar 

  • Gentile CL, Nivala AM, Gonzales JC, Pfaffenbach KT, Wang D, Wei Y, Jiang H, Orlicky DJ, Petersen DR, Pagliassotti MJ, Maclean KN (2011) Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease. Am J Physiol Regul Integr Comp Physiol 301:R1710–1722

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Huxtable RJ (1992) Physiological actions of taurine. Physiol Rev 72:101–163

    Article  PubMed  CAS  Google Scholar 

  • Hwang DF, Wang LC, Cheng HM (1998) Effect of taurine on toxicity of copper in rats. Food Chem Toxicol 36:239–244

    Article  PubMed  CAS  Google Scholar 

  • Ibrahim SH, Hirsova P, Malhi H, Gores GJ (2016) Animal models of nonalcoholic steatohepatitis: eat, delete, and inflame. Dig Dis Sci 61:1325–1336

    Article  PubMed  Google Scholar 

  • Ito T, Yoshikawa N, Ito H, Schaffer SW (2015) Impact of taurine depletion on glucose control and insulin secretion in mice. J Pharmacol Sci 129:59–64

    Article  PubMed  CAS  Google Scholar 

  • James AM, Collins Y, Logan A, Murphy MP (2012) Mitochondrial oxidative stress and the metabolic syndrome. Trends Endocrinol Metab 23:429–434

    Article  PubMed  CAS  Google Scholar 

  • Jong CJ, Azuma J, Schaffer S (2012) Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids 42:2223–2232

    Article  PubMed  CAS  Google Scholar 

  • Kerai MD, Waterfield CJ, Kenyon SH, Asker DS, Timbrell JA (1998) Taurine: protective properties against ethanol-induced hepatic steatosis and lipid peroxidation during chronic ethanol consumption in rats. Amino Acids 15:53–76

    Article  PubMed  CAS  Google Scholar 

  • Lazo M, Clark JM (2008) The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis 28:339–350

    Article  PubMed  Google Scholar 

  • Lin S, Hirai S, Yamaguchi Y, Goto T, Takahashi N, Tani F, Mutoh C, Sakurai T, Murakami S, Yu R, Kawada T (2013) Taurine improves obesity-induced inflammatory responses and modulates the unbalanced phenotype of adipose tissue macrophages. Mol Nutr Food Res 57:2155–2165

    Article  PubMed  CAS  Google Scholar 

  • Liu W, Baker SS, Baker RD, Zhu L (2015) Antioxidant mechanisms in nonalcoholic fatty liver disease. Curr Drug Targets 16:1301–1314

    Article  PubMed  CAS  Google Scholar 

  • Murakami S, Yamagishi I, Asami Y, Ohta Y, Toda Y, Nara Y, Yamori Y (1996) Hypolipidemic effect of taurine in stroke-prone spontaneously hypertensive rats. Pharmacology 52:303–313

    Article  PubMed  CAS  Google Scholar 

  • Murakami S, Yamagishi I, Sato M, Tomisawa K, Nara Y, Yamori Y (1997) ACAT inhibitor HL-004 accelerates the regression of hypercholesterolemia in stroke-prone spontaneously hypertensive rats (SHRSP): stimulation of bile acid production by HL-004. Atherosclerosis 133:97–104

    Article  PubMed  CAS  Google Scholar 

  • Murakami S, Kondo-Ohta Y, Tomisawa K (1999) Improvement in cholesterol metabolism in mice given chronic treatment of taurine and fed a high-fat diet. Life Sci 64:83–91

    Article  PubMed  CAS  Google Scholar 

  • Murakami S, Kondo Y, Toda Y, Kitajima H, Kameo K, Sakono M, Fukuda N (2002) Effect of taurine on cholesterol metabolism in hamsters: up-regulation of low density lipoprotein (LDL) receptor by taurine. Life Sci 70:2355–2366

    Article  PubMed  CAS  Google Scholar 

  • Murakami S, Sakurai T, Tomoike H, Sakono M, Nasu T, Fukuda N (2010) Prevention of hypercholesterolemia and atherosclerosis in the hyperlipidemia- and atherosclerosis-prone Japanese (LAP) quail by taurine supplementation. Amino Acids 38:271–278

    Article  PubMed  CAS  Google Scholar 

  • Murakami S, Fujita M, Nakamura M, Sakono M, Nishizono S, Sato M, Imaizumi K, Mori M, Fukuda N (2016) Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats. Clin Exp Pharmacol Physiol 43:372–378

    Article  PubMed  CAS  Google Scholar 

  • Parvez S, Tabassum H, Banerjee BD, Raisuddin S (2008) Taurine prevents tamoxifen-induced mitochondrial oxidative damage in mice. Basic Clin Pharmacol Toxicol 102:382–387

    Article  PubMed  CAS  Google Scholar 

  • Schaffer SW, Jong CJ, Ito T, Azuma J (2014) Role of taurine in the pathologies of MELAS and MERRF. Amino Acids 46:47–56

    Article  PubMed  CAS  Google Scholar 

  • Shimada K, Jong CJ, Takahashi K, Schaffer SW (2015) Role of ROS production and turnover in the antioxidant activity of taurine. Adv Exp Med Biol 803:581–596

    Article  PubMed  CAS  Google Scholar 

  • Spahis S, Delvin E, Borys JM, Levy E (2017) Oxidative stress as a critical factor in nonalcoholic fatty liver disease pathogenesis. Antioxid Redox Signal 26:519–541

    Article  PubMed  CAS  Google Scholar 

  • Stojsavljević S, Gomerčić Palčić M, Virović Jukić L, Smirčić Duvnjak L, Duvnjak M (2014) Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol 20:18070–18091

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Suzuki T, Suzuki T, Wada T, Saigo K, Watanabe K (2002) Taurine as a constituent of mitochondrial tRNAs: new insights into the functions of taurine and human mitochondrial diseases. EMBO J 21:6581–6589

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tsuboyama-Kasaoka N, Shozawa C, Sano K, Kamei Y, Kasaoka S, Hosokawa Y, Ezaki O (2006) Taurine (2-aminoethanesulfonic acid) deficiency creates a vicious circle promoting obesity. Endocrinology 147:3276–3284

    Article  PubMed  CAS  Google Scholar 

  • Waters E, Wang JH, Redmond HP, Wu QD, Kay E, Bouchier-Hayes D (2001) Role of taurine in preventing acetaminophen-induced hepatic injury in the rat. Am J Physiol Gastrointest Liver Physiol 280:G1274–1279

    Article  PubMed  CAS  Google Scholar 

  • Yokogoshi H, Mochizuki H, Nanami K, Hida Y, Miyachi F, Oda H (1999) Dietary taurine enhances cholesterol degradation and reduces serum and liver cholesterol concentrations in rats fed a high-cholesterol diet. J Nutr 129:1705–1712

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Shigeru Murakami.

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The authors declare no conflicts of interest in association with the present study.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Handling Editor: S. W. Schaffer.

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Murakami, S., Ono, A., Kawasaki, A. et al. Taurine attenuates the development of hepatic steatosis through the inhibition of oxidative stress in a model of nonalcoholic fatty liver disease in vivo and in vitro. Amino Acids 50, 1279–1288 (2018). https://doi.org/10.1007/s00726-018-2605-8

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  • DOI: https://doi.org/10.1007/s00726-018-2605-8

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