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트레이닝 강도가 고지방식이로 유도된 마우스 지방간과 miRNAs 및 표적 유전자 발현에 미치는 영향

Effect of Training Intensity on Hepatic Steatosis and Expression of miRNAs and Target Genes in a High-fat Diet-induced Mice

박인호|윤진환|강현식|조진경
한국운동생리학회|2018.02|운동과학 (Exercise Science)|제27권 제1호|pp. 32-39|DOI https://doi.org/10.15857/ksep.2018.27.1.32

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참고문헌

키워드

운동강도Exercise intensitymicroRNA트레드밀 운동Treadmill runningNon-alcoholic fatty liver비알코올성 지방간

초록

PURPOSE: This study investigated the effect of exercise intensity on hepatic microRNA (miRNA) expression in a high-fat diet (HFD)- induced obese mice. METHODS: A total of 40 male C57BL/6 mice aged 5 weeks were randomly subjected to either standard chow (SC, n=10) or HFD (HFD, n=30) for 23 weeks. After 8 weeks of dietary treatments, mice in the HFD group were further divided and subjected to either HFD only (n=10) or HFD with high-intensity interval treadmill running (HFD+INT, n=10) or HFD with moderate-intensity treadmill running (HFD+MOD) for additional 15 weeks. Hepatic total RNA was extracted to analyze global expression profiles of miRNAs, which was followed by real-time PCR to quantify hepatic expressions of up or down-regulated miRNAs and mRNAs. RESULTS: As expected, chronic exposure to HFD resulted in obesity and hepatic steatosis in conjunction with increased serum concentrations of total cholesterol, aspartate transaminase, and alanine transaminase. In addition, HFD resulted in upregulation of hepatic miR-149 and miR-34a levels in conjunction with downregulation of hepatic peroxisome proliferator-activated receptor alpha (PPAR-α) and sirtuin1 (SIRT1) mRNAs. On the other hand, exercise training, especially high-intensity interval training, attenuated the liver damage and total cholesterol in conjunction with downregulation of hepatic miR-149 and miR-34a levels and upregulation of hepatic PPAR-α and SIRT1 mRNAs. CONCLUSIONS: This study suggests that exercise training, especially performed at a high-intensity, was effective in attenuating HFDinduced- fatty liver phenotypes as well as HFD–induced dysregulation of miRNAs in the liver.

Abstract

PURPOSE: This study investigated the effect of exercise intensity on hepatic microRNA (miRNA) expression in a high-fat diet (HFD)- induced obese mice. METHODS: A total of 40 male C57BL/6 mice aged 5 weeks were randomly subjected to either standard chow (SC, n=10) or HFD (HFD, n=30) for 23 weeks. After 8 weeks of dietary treatments, mice in the HFD group were further divided and subjected to either HFD only (n=10) or HFD with high-intensity interval treadmill running (HFD+INT, n=10) or HFD with moderate-intensity treadmill running (HFD+MOD) for additional 15 weeks. Hepatic total RNA was extracted to analyze global expression profiles of miRNAs, which was followed by real-time PCR to quantify hepatic expressions of up or down-regulated miRNAs and mRNAs. RESULTS: As expected, chronic exposure to HFD resulted in obesity and hepatic steatosis in conjunction with increased serum concentrations of total cholesterol, aspartate transaminase, and alanine transaminase. In addition, HFD resulted in upregulation of hepatic miR-149 and miR-34a levels in conjunction with downregulation of hepatic peroxisome proliferator-activated receptor alpha (PPAR-α) and sirtuin1 (SIRT1) mRNAs. On the other hand, exercise training, especially high-intensity interval training, attenuated the liver damage and total cholesterol in conjunction with downregulation of hepatic miR-149 and miR-34a levels and upregulation of hepatic PPAR-α and SIRT1 mRNAs. CONCLUSIONS: This study suggests that exercise training, especially performed at a high-intensity, was effective in attenuating HFDinduced- fatty liver phenotypes as well as HFD–induced dysregulation of miRNAs in the liver.

참고문헌 (35)

  1. Matteoni CA, "Nonalcoholic fatty liver disease : a spectrum of clinical and pathological severity", Gastroenterology, 116(6), pp.1413~1419 (1999)
  2. Kovalic AJ, "The role of nonalcoholic fatty liver disease on cardiovascular manifestations and outcomes", Clin Liver Dis, 22(1), pp.141~174 (2018)
  3. Park SH, "Prevalence and risk factors of non-alcoholic fatty liver disease among Korean adults", J Gastroenterol Hepatol, 21(1), pp.138~143 (2006)
  4. Postic C, "Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance : lessons from genetically engineered mice", J Clin Invest, 118(3), pp.829~838 (2008)
  5. Donnelly KL, "Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease", J Clin Invest, 115(5), pp.1343~1351 (2005)
  6. Lee SS, "Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators", Mol Cell Biol, 15(6), pp.3012~3022 (1995)
  7. Colak Y, "SIRT1 as a potential therapeutic target for treatment of nonalcoholic fatty liver disease", Med Sci Monit, 17(5), pp.HY5~9 (2011)
  8. Sayed D, "Micrornas in development and disease", Physiol. Rev, 91(3), pp.827~887 (2011)
  9. Kim VN, "Biogenesis of small rnas in animals", Nature Reviews Molecular Cell Biology, 10(2), pp.126~139 (2009)
  10. Carthew RW, "Origins and mechanisms of mirnas and sirnas", Cell, 136(4), pp.642~655 (2009)
  11. Xiao J, "MicroRNA-204 is required for differentiation of human-derived cardiomyocyte progenitor cells", J Mol Cell Cardiol, 53(6), pp.751~759 (2012)
  12. Yamada H, "Longitudinal study of circulating mir-122 in a rat model of non-alcoholic fatty liver disease", Clinica Chimica Acta, 446, pp.267~271 (2015)
  13. Hur W, "Downregulation of microrna-451 in non-alcoholic steatohepatitis inhibits fatty acid-induced proinflammatory cytokine production through the ampk", akt pathway, 2015, pp.64, 265~276
  14. Panera N, "MicroRNAs as controlled systems and controllers in non-alcoholic fatty liver disease", World J Gastroenterol, 20(41), pp.15079~15086 (2014)
  15. Yamada H, "Associations between circulating microRNAs(miR-21, miR-34a, miR-122 and miR-451)and non-alcoholic fatty liver", Clinica Chimica Acta, 424, pp.99~103 (2013)
  16. Cheung O, "Nonalcoholic steatohepatitis is associated with altered hepatic microRNA expression", Hepatology, 48(6), pp.1810~1820 (2008)
  17. Castro RE, "Mir-34a", SIRT1, J Hepatol, pp.2013, 58(1)[DOI]
  18. Eliosoff R, "Intensive lifestyle intervention in type 2 diabetes", N Eng J Med, 369(24), pp.2357~2358 (2013)
  19. Lucia A, "Muscling in on cancer", N Engl J Med, 375(9), pp.892~894 (2016)
  20. Garatachea N, "Elite athletes live longer than the general population : a meta-analysis", Mayo Clin Proc, 89(9), pp.1195~1200 (2014)
  21. Lee IM, "Effect of physical inactivity on major non-communicable diseases worldwide : an analysis of burden of disease and life expectancy", The Lancet, 380(9838), pp.219~229 (2012)
  22. Church TS, "Association of cardiorespiratory fitness, body mass index, and waist circumference to nonalcoholic fatty liver disease", Gastroenterology, 130(7), pp.2023~2030 (2006)
  23. Cho J, "Effect of Training Intensity on Nonalcoholic Fatty Liver Disease", Med Sci Sports Exerc, 47(8), pp.1624~1634 (2015)
  24. Meng F, "Epigenetic Regulation of miR-34a Expression in Alcoholic Liver Injury", Am J Pathol, 181(3), pp.804~817 (2012)
  25. Li WQ, "The rno-miR-34 family is upregulated and targets ACSL1 in dimethylnitrosamine-induced hepatic fibrosis in rats", The FEBS Journal, 278(9), pp.1522~1532 (2011)
  26. Cai H, "MiRNA expression profiles reveal the involvement of miR-26a, miR-548l and miR-34a in hepatocellular carcinoma progression through regulation of ST3GAL5", Laboratory Investigation, 97(5), pp.530~542 (2017)
  27. Ding J, "Effect of miR-34a in regulating steatosis by targeting PPARα expression in nonalcoholic fatty liver disease", Scientific Reports, 5, pp.13729~ (2015)
  28. Choi SE, "Elevated microRNA-34a in obesity reduces NAD+ levels and SIRT1 activity by directly targeting NAMPT", Aging Cell, 12(6), pp.1062~1072 (2013)
  29. Xiao J, "miR-149 controls non-alcoholic fatty liver by targeting FGF-21", J Cell Mol Med, 20(8), pp.1603~1608 (2016)
  30. Xiao J, "miR-212downregulation contributes to the protective effect of exercise against non-alcoholic fatty liver via targeting FGF-21", J Cell Mol Med, 20(2), pp.204~216 (2016)
  31. Francis GA, "Nuclear receptors and the control of metabolism", Annu Rev Physiol, 65(1), pp.261~311 (2003)
  32. Seo YS, "PPAR agonists treatment is effective in a nonalcoholic fatty liver disease animal model by modulating fatty-acid metabolic enzymes", J Gastroenterol Hepatol, 23(1), pp.102~109 (2008)
  33. Wang N, "High-intensity interval versus moderate-intensity continuous training : Superior metabolic benefits in dietinduced obesity mice", Life Sci, 191, pp.122~131 (2017)
  34. Guarente, "Sirtuins as potential targets for metabolic syndrome", Nature, 444(7121), pp.868~874 (2006)
  35. Gerhart-Hines Z, "Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1", PGC-1alpha, 2007, pp.26(7), 1913~1923

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