Relative Gene Expression of Key Genes Involved in Lipid Metabolism, Following High Fat Diet and Moderate and High Intensity Aerobic Training in Rat’s Liver

Document Type : Research Paper

Authors

1 Ph.D. in Exercise Biochemistry and Metabolism, University of Mazandaran

2 Associate Professor of Exercise Biochemistry and Metabolism, University of Mazandaran

3 Associate Professor of Animal Science, Sari Agricultural Sciences & Natural Resources University

Abstract
To study the hepatic lipid metabolism, 44 male Wistar rats randomly divided in two normal or high fat diet groups. Each group was included of control, moderate exercise and high intensity exercise groups. After the 8 weeks of training hepatic relative gene expression of Farnesoid X Receptor (FXR), Peroxisome proliferator activated receptor alpha (PPAR-α) and also sterol regulatory element binding protein 1c (SREBP-1c) were assessed. Also, plasma lipid profile and Aminotransferases levels were measured. Data were analyzed by 2way ANOVA in SPSS 22 (P<0.05). According to the results, high fat diet caused dyslipidemia and probably liver injury and only increased SERBP-1crelative gene expression. Although training had not any effect on FXR expression, PPAR-α expression increased in trained high fat diet groups, independent to intensity. SREBP-1c expression just decreased by high intensity training in normal diet group. In summary, dyslipidemia and hepatic fat overload could be induced by high fat diet due to hepatic SREBP-1c expression and activation of lipogenic pathways. Although exercise changed the gene expression but had no effect on lipid profile or transaminases. 

Keywords

Main Subjects

  1. Baidal J A, Lavine J E. The intersection of nonalcoholic fatty liver disease and obesity. Sci Transl Med. 2016‌; 8(323): 323rv1‌.
  2. Hong Sh, Ahmadian M, Ruth T Y, Atkins A R, Downes M, Evans R M. Nuclear receptors and metabolism: From feast to famine. Diabetologia. 2014‌; 57(5):    860-7.
  3. Shiomi Y, Yamauchi T, Iwabu M, Okada-Iwabu M, Nakayama R, Orikawa Y, et al. A novel peroxisome proliferator-activated receptor (PPAR) α agonist and PPARγ antagonist, Z-551, ameliorates high-fat diet-induced obesity and metabolic disorders in Mice. J Biol Chem. 2015; 290(23): 14567-81.
  4. Fiorucci S, Cipriani S, Baldelli F, Mencarelli A. Bile acid-activated receptors in the treatment of dyslipidemia and related disorders. Prog Lipid Res. 2010‌; 49(2): 171-85.
  5. Derosa G, Maffioli P. Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists on glycemic control, lipid profile and cardiovascular risk. Curr Mol Pharmacol. 2012; 5(2): 272-81.
  6. Cintra D E, Ropelle E R, Vitto M F, Luciano T F, Souza D R, Engelmann J, et al. Reversion of hepatic steatosis by exercise training in obese mice: The role of sterol regulatory element-binding protein-1c. Life Sci. 2012‌; 91(11): 395-401.
  7. Capel F, Rolland-Valognes G, Dacquet C, Brun M, Lonchampt M, Ktorza A, et al. Analysis of sterol-regulatory element-binding protein 1c target genes in mouse liver during aging and high-fat diet. J Nutrigenet Nutrigenomics. 2013‌; 6(2):  107-22.
  8. Xu J Y, Li Z P, Zhang L, Ji G. Recent insights into farnesoid X receptor in non-alcoholic fatty liver disease. World J Gastroenterol: WJG. 2014‌; 20(37): 13493.
  9. Chennamsetty I, Claudel T, Kostner K M, Baghdasaryan A, Kratky D, Levak-Frank S, et al. Farnesoid X receptor represses hepatic human APOA gene expression. J Clin Invest. 2011; 121(9): 3724-34.
  10. Evans R M, Barish G D, Wang Y X. PPARs and the complex journey to obesity. Nat Med. 2004‌; 10(4): 355-61.
  11. Jiao Y, Lu Y, Li X Y. Farnesoid X receptor: A master regulator of hepatic triglyceride and glucose homeostasis. Acta Pharmacol Sin. 2015‌; 36(1)‌: 44-50.
  12. Wen S, Jadhav K S, Williamson D L, Rideout T C. Treadmill exercise training modulates hepatic cholesterol metabolism and circulating PCSK9 concentration in high-fat-fed mice. J lipids. 2013‌;‌
  13. Xu Z J, Fan J G, Ding X D, Qiao L, Wang G L. Characterization of high-fat, diet-induced, non-alcoholic steatohepatitis with fibrosis in rats. Dig Dis Sci. 2010‌; 55(4): 931-40.
  14. Hawley J A, Yeo W K. Metabolic adaptations to a high‐fat diet. The Encyclopaedia of Sports Medicine: An IOC Medical Commission Publication. 2014; 19: 166-73.
  15. Hosseini Kakhk A, Khalegh Zadeh H, Nemati M, Hamedi Nia M. The effect of combined aerobic‌-‌‌resistance training on lipid profile and liver enzymes in patients with non-alcoholic fatty liver under nutrition diet. Sport Physiology. 2015; 7(27): 65-84. (In Persian).
  16. Sarlak Z. Effects of eight weeks aerobic training on Serum Apo A-I‌, APO B and lipid profile in overweight women. Sport Physiology. 2016; 7(28): 45-58.             (In Persian).
  17. Sookoian S, Pirola C J. Alanine and aspartate aminotransferase and glutamine-cycling pathway: Their roles in pathogenesis of metabolic syndrome. World J Gastroenterol. 2012; 18(29): 3775-81.
  18. Sookoian S, Pirola C J. Liver enzymes, metabolomics and genome-wide association studies: From systems biology to the personalized medicine. World J Gastroenterol. 2015; 21(3): 711-25.
  19. Bishop‐Bailey D. Mechanisms governing the health and performance benefits of exercise. Br J Pharmacol. 2013‌; 170(6): 1153-66.
  20. Srinivasan K, Viswanad B, Asrat L, Kaul C L, Ramarao P. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: A model for type 2 diabetes and pharmacological screening. Pharmacol Res. 2005‌; 52(4): 313-20.
  21. Bustin S A, Benes V, Garson J A, Hellemans J, Huggett J, Kubista M, et al. The Miqe guidelines: Minimum information for publication of quantitative real-time PCR experiments. ‎Clin Chem. 2009‌; 55(4): 611-22.
  22. Côté I, Sock E T, Lévy É, Lavoie J M. An atherogenic diet decreases liver FXR gene expression and causes severe hepatic steatosis and hepatic cholesterol accumulation: Effect of endurance training. Eur J Clin Nutr. 2013‌; 52(5):        1523-32.
  23. Marques C M, Motta V F, Torres T S, Aguila M B, Mandarim-de-Lacerda C A. Beneficial effects of exercise training (treadmill) on insulin resistance and nonalcoholic fatty liver disease in high-fat fed C57BL/6 mice. Braz J Med Biol Res. 2010‌; 43(5): 467-75.
  24. Otunola G A, Oloyede O B, Oladiji A T, Afolayan A A. Effects of diet-induced hypercholesterolemia on the lipid profile and some enzyme activities in female Wistar rats. Afr J Biochem Res. 2010‌; 4(6): 149-54.
  25. Fu L, Liu X, Niu Y, Yuan H, Zhang N, Lavi E. Effects of high-fat diet and regular aerobic exercise on global gene expression in skeletal muscle of C57BL/6 mice. Metabolism. 2012; 61(2): 146-52.
  26. Ichimura M, Kawase M, Masuzumi M, Sakaki M, Nagata Y, Tanaka K, et al. High‐fat and high‐cholesterol diet rapidly induces non‐alcoholic steatohepatitis with advanced fibrosis in Sprague–Dawley rats. Hepatol Res. 2015‌; 45(4):       458-69.
  27. Jacob P S, Meneses Fujii T M, Yamada M, Borges M C, Pantaleao L C, Borelli P, et al. Isocaloric intake of a high‐fat diet promotes insulin resistance and inflammation in Wistar rats. Cell Biochem Funct. 2013‌; 31(3): 244-53.
  28. Carmiel-Haggai M, Cederbaum A I, Nieto N. A high-fat diet leads to the progression of non-alcoholic fatty liver disease in obese rats. FASEB J. 2005‌; 19(1): 136-8.
  29. Cameron I, Alam M A, Wang J, Brown L. Endurance exercise in a rat model of metabolic syndrome. Can J Physiol Pharmacol. 2012‌; 90(11): 1490-7.
  30. Keating S E, Hackett D A, George J, Johnson N A. Exercise and non-alcoholic fatty liver disease: A systematic review and meta-analysis. J Hepatol. 2012‌; 57(1): 157-66.
  31. Yang Z, Cappello T, Wang L. Emerging role of microRNAs in lipid metabolism. Acta Pharm Sin B. 2015‌; 5(2): 145-50.
  32. Gadaleta R M, Cariello M, Sabbà C, Moschetta A. Tissue-specific actions of FXR in metabolism and cancer. ‎Biochim Biophys Acta (32)-Molecular and Cell Biology of Lipids. 2015; 1851(1): 30-9.
  33. Oshida K, Vasani N, Thomas R S, Applegate D, Rosen M, Abbott B, et al. Identification of modulators of the nuclear receptor peroxisome proliferator-activated receptor α (PPARα) in a mouse liver gene expression compendium. PloS one. 2015‌; 10(2): e0112655.
  34. Wu H, Jin M, Han D, Zhou M, Mei X, Guan Y, et al. Protective effects of aerobic swimming training on high-fat diet induced nonalcoholic fatty liver disease: Regulation of lipid metabolism via PANDER-AKT pathway. Biochem Biophys Res Commun. 2015; 458(4): 862-8.
  35. Bosma M. Lipid homeostasis in exercise. Drug Discov Today. 2014‌; 19(7):   1019-23.
  36. Hsu W H, Chen T H, Lee B H, Hsu Y W, Pan T M. Monascin and ankaflavin act as natural AMPK activators with PPARα agonist activity to down-regulate nonalcoholic steatohepatitis in high-fat diet-fed C57BL/6 mice. Food Chem Toxicol. 2014‌; 64: 94-103.
  37. Karagianni P, Talianidis I. Transcription factor networks regulating hepatic fatty acid metabolism. Biochim Biophys Acta (32)-Molecular and Cell Biology of Lipids. 2015; 1851(1): 2-8.
Sport Physiology
Volume 9, Issue 34 - Serial Number 34
Summer 2017
July 2017
Pages 201-216

  • Receive Date 17 July 2016
  • Revise Date 03 October 2016
  • Accept Date 15 October 2016