Resveratrol reduces lipid accumulation through upregulating the expression of microRNAs regulating fatty acid bet oxidation in liver cells: Evidence from in vivo and in vitro studies

Document Type : Research article

Authors

1 Department of Clinical Biochemistry, Medicine Faculty, Tehran University of Medical Sciences, Tehran, Iran.

2 Recombinant Protein Laboratory, Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz, Iran.

3 Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

4 Department of Clinical biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

MicroRNAs has been shown to regulate lipogenesis in liver. The aim of the present study was to investigate whether the effects of resveratrol (RSV) on lipogenesis is associated with the changes in the expression of two miRNAs (miR-107 and miR-10b) that regulate lipogenic pathways. 30 wild type C57BL/6j male mice were randomly fed three diets: a standard chow diet (ND), a high fat diet (HFD, 60% fat) and the high fat diet supplemented with 0.4% RSV (HFD-RSV) for 16 weeks. HepG2 cells were treated with high glucose (33mM) and RSV (20µM) for 24 h. The expression of the genes and miRNAs were measured by real-time PCR. Triglyceride level was increased in the liver of mice and HepG2 cells. In both animal and in vitro experiments, triglyceride level was significantly decreased in groups treated with RSV. The expression of the miR-107 and miR-10b was significantly upregulated in the liver of HFD mice, whereas HFD-RSV group demonstrated a significant lower expression of both miRNAs compared to HFD group. In addition, RSV treatment significantly upregulated the expression of CPT-1a and PPARα genes in the liver of HFD mice. Moreover, treatment with RSV could reduce the expression of miR-107 and miR-10b and increase the expression of CPT-1a and PPARα in HG-treated HepG2 cells. These evidence, as a whole, suggest that RSV could exert its anti-lipogenic effect partially through alterations in the expression of miR-107 and miR-10b in liver cells.

Graphical Abstract

Resveratrol reduces lipid accumulation through upregulating the expression of microRNAs regulating fatty acid bet oxidation in liver cells: Evidence from in vivo and in vitro studies

Keywords

References

  1. Kopelman, P.G.J.N., Obesity as a medical problem. 2000. 404(6778): p. 635.
  2. Tiniakos, D.G., M.B. Vos, and E.M.J.A.R.o.P.M.D. Brunt, Nonalcoholic fatty liver disease: pathology and pathogenesis. 2010. 5: p. 145-171.
  3. Méndez‐Sánchez, N., et al., Current concepts in the pathogenesis of nonalcoholic fatty liver disease. 2007. 27(4): p. 423-433.
  4. Qureshi, K. and G.A.J.W.j.o.g.W. Abrams, Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease. 2007. 13(26): p. 3540.
  5. Sanyal, A.J.J.G., AGA technical review on nonalcoholic fatty liver disease. 2002. 123(5): p. 1705-1725.
  6. Satapathy, S.K. and A.J. Sanyal. Epidemiology and natural history of nonalcoholic fatty liver disease. in Seminars in liver disease. 2015. Thieme Medical Publishers.
  7. Jones, C.I. and S.F. Newbury, Functions of microRNAs in Drosophila development. 2010, Portland Press Limited.
  8. Amiel, J. and A.J.A.i.g. Henrion-Caude, miRNA, development and disease. 2012. 80: p. 1-36.
  9. Jansson, M.D. and A.H.J.M.o. Lund, MicroRNA and cancer. 2012. 6(6): p. 590-610.
  10. Bhatia, H., B.R. Pattnaik, and M. Datta, Inhibition of mitochondrial beta-oxidation by miR-107 promotes hepatic lipid accumulation and impairs glucose tolerance in vivo. Int J Obes (Lond), 2016. 40(5): p. 861-9.
  11. Gracia, A., et al., Are mirna-103, mirna-107 and mirna-122 involved in the prevention of liver steatosis induced by resveratrol? 2017. 9(4): p. 360.
  12. Zheng, L., et al., Effect of miRNA‐10b in regulating cellular steatosis level by targeting PPAR‐α expression, a novel mechanism for the pathogenesis of NAFLD. 2010. 25(1): p. 156-163.
  13. Koushki, M., et al., Resveratrol: A miraculous natural compound for diseases treatment. 2018. 6(8): p. 2473-2490.
  14. Smoliga, J.M., et al., Resveratrol and health–a comprehensive review of human clinical trials. 2011. 55(8): p. 1129-1141.
  15. Gawlik, K., et al., Markers of antioxidant defense in patients with type 2 diabetes. Oxidative medicine and cellular longevity, 2015. 2016.
  16. Rayalam, S., et al., Resveratrol induces apoptosis and inhibits adipogenesis in 3T3‐L1 adipocytes. 2008. 22(10): p. 1367-1371.
  17. Li, S., et al., Resveratrol inhibits lipogenesis of 3T3-L1 and SGBS cells by inhibition of insulin signaling and mitochondrial mass increase. 2016. 1857(6): p. 643-652.
  18. Lasa, A., et al., Resveratrol regulates lipolysis via adipose triglyceride lipase. 2012. 23(4): p. 379-384.
  19. Mercader, J., A. Palou, and M.L.J.T.J.o.n.b. Bonet, Resveratrol enhances fatty acid oxidation capacity and reduces resistin and Retinol-Binding Protein 4 expression in white adipocytes. 2011. 22(9): p. 828-834.
  20. Davinelli, S., et al., Enhancement of mitochondrial biogenesis with polyphenols: combined effects of resveratrol and equol in human endothelial cells. 2013. 10(1): p. 28.
  21. Hwang, J.-T., et al., Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase. 2005. 338(2): p. 694-699.
  22. Izdebska, M., et al., Resveratrol Limits Lipogenesis and Enhance Mitochondrial Activity in HepG2 Cells. 2018. 21(1): p. 504-515.
  23. Mohammadpou, Z., et al., Resveratrol suppresses hyperglycemia-induced activation of NF-κB and AP-1 via c-Jun and RelA gene regulation. 2018. 32: p. 10.
  24. Hirako, S., et al., Low-dose fish oil consumption prevents hepatic lipid accumulation in high cholesterol diet fed mice. 2011. 59(24): p. 13353-13359.
  25. Marchesini, G., et al., Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. 2001. 50(8): p. 1844-1850.
  26. Cheung, O., et al., Nonalcoholic steatohepatitis is associated with altered hepatic MicroRNA expression. Hepatology, 2008. 48(6): p. 1810-20.
  27. Wilfred, B.R., et al., Energizing miRNA research: a review of the role of miRNAs in lipid metabolism, with a prediction that miR-103/107 regulates human metabolic pathways. 2007. 91(3): p. 209-217.
  28. Li, S., et al., Differential expression of microRNAs in mouse liver under aberrant energy metabolic status. Journal of lipid research, 2009. 50(9): p. 1756-1765.
  29. Trajkovski, M., et al., MicroRNAs 103 and 107 regulate insulin sensitivity. Nature, 2011. 474(7353): p. 649.
  30. Kornfeld, J.-W., et al., Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b. Nature, 2013. 494(7435): p. 111.
  31. Foley, N.H. and L.A. OˈNeill, miR‐107: a Toll‐like receptor‐regulated miRNA dysregulated in obesity and type II diabetes. Journal of leukocyte biology, 2012. 92(3): p. 521-527.
  32. Polvani, S., et al., Peroxisome proliferator activated receptors at the crossroad of obesity, diabetes, and pancreatic cancer. World journal of gastroenterology, 2016. 22(8): p. 2441.
  33. Pawlak, M., P. Lefebvre, and B. Staels, Molecular mechanism of PPARα action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. Journal of hepatology, 2015. 62(3): p. 720-733.
  34. Francis, G.A., J.-S. Annicotte, and J. Auwerx, PPAR-α effects on the heart and other vascular tissues. American Journal of Physiology-Heart and Circulatory Physiology, 2003. 285(1): p. H1-H9.
  35. Lee, G.Y., et al., Peroxisomal-proliferator-activated receptor alpha activates transcription of the rat hepatic malonyl-CoA decarboxylase gene: a key regulation of malonyl-CoA level. Biochemical Journal, 2004. 378(3): p. 983-990.
  36. Portius, D., C. Sobolewski, and M. Foti, MicroRNAs-Dependent Regulation of PPARs in Metabolic Diseases and Cancers. PPAR Research, 2017. 2017: p. 19.
Iranian Journal of Pharmaceutical Research
Volume 19, Issue 2
Spring 2020
Pages 333-340

Files

Share

How to cite

Statistics