The Effect of Endurance Training and High-Fat Diet on PGC-1a/FNDC5/Irisin Pathway in Male C57BL/6 Mice

Document Type : Research Paper

Authors
Fatemeh Kazemi Nasab 1
Mohammad Marandi 2
Kamran Ghaedi 3
Fahimeh Esfarjani 4
Mohammad Hossein Nasr-Esfahani 5
1 Ph.D. Student of Exercise Physiology, University of Isfahan
2 Professor of Exercise Physiology, University of Isfahan
3 Professor of Biology, University of Isfahan
4 Associate Professor of Exercise Physiology, University of Isfahan
5 Professor of Embryology, Royan Institute for Biotechnology
10.22089/spj.2017.4295.1573
Abstract
The purpose of this study was to investigate the effect of endurance training and high fat diet on PGC-1a/FNDC5/Irisin pathway in Gastrocnemius muscle and visceral adipose tissue in male C57BL/6 mice. Male C57BL/6 mice were divided to 4 groups: High fat-Exercise (HF-E), High fat-Sedentary (HF-S), Low fat-Exercise (LF-E) and Low fat-Sedentary (LF-S). Exercise groups received exercise on a motor-driven treadmill at 21m/min, 45 min/day, 5 days/week for 8 weeks. 24 hours after final exercise session, mice were sacrificed and blood samples were taken from the mice to measure plasma irisin. Gastrocnemius skeletal muscle and visceral adipose tissue were excised and frozen in liquid nitrogen for assessment of PGC-1a and FNDC5 mRNA levels. Data was analyzed by a two-way ANOVA at P0.05). The results of this study indicate that high fat diet increases the expression of FNDC5 in the Gastrocnemius muscle tissue. Also, there is a potential correlation between the expression of muscular FNDC5 and body fat mass, which requires further studies to investigate its cellular and molecular mechanisms.
Keywords
High-Fat Diet
Endurance Training
PGC-1a mRNA
FNDC5 mRNA
Irisin

Main Subjects

  1. Al-Daghri NM, Mohammed AK, Al-Attas OS, Amer OE, Clerici M, Alenad A, et al. SNPs in FNDC5 (irisin) are associated with obesity and modulation of glucose and lipid metabolism in Saudi subjects. Lipids Health Dis. 2016;15:54. 1-8.
  2. Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463-8.
  3. Norheim F, Langleite TM, Hjorth M, Holen T, Kielland A, Stadheim HK, et al. The effects of acute and chronic exercise on PGC-1alpha, irisin and browning of subcutaneous adipose tissue in humans. FEBS J. 2014;281(3):739-49.
  4. Nygaard H, Slettalokken G, Vegge G, Hollan I, Whist JE, Strand T, et al. Irisin in blood increases transiently after single sessions of intense endurance exercise and heavy strength training. PLoS One. 2015;10(3):e0121367.
  5. Wu MV, Bikopoulos G, Hung S, Ceddia RB. Thermogenic capacity is antagonistically regulated in classical brown and white subcutaneous fat depots by high fat diet and endurance training in rats: Impact on whole-body energy expenditure. J Biol Chem. 2014;289(49):34129-40.
  6. Elsen M, Raschke S, Eckel J. Browning of white fat: Does irisin play a role in humans? J Endocrinol. 2014;222(1):R25-38.
  7. Seale P, Kajimura S, Yang W, Chin S, Rohas LM, Uldry M, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab. 2007;6(1):38-54.
  8. Ellefsen S, Vikmoen O, Slettalokken G, Whist JE, Nygaard H, Hollan I, et al. Irisin and FNDC5: Effects of 12-week strength training, and relations to muscle phenotype and body mass composition in untrained women. Eur J Appl Physiol. 2014;114(9):1875-88.
  9. Bang HS, Seo DY, Chung YM, Oh KM, Park JJ, Arturo F, et al. Ursolic Acid-induced elevation of serum irisin augments muscle strength during resistance training in men. Korean J Physiol Pharmacol. 2014;18(5):441-6.
  10. Moreno-Navarrete JM, Ortega F, Serrano M, Guerra E, Pardo G, Tinahones F, et al. Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. J Clin Endocrinol Metab. 2013;98(4):e769-78.
  11. Sanchis-Gomar F, Alis R, Pareja-Galeano H, Sola E, Victor VM, Rocha M, et al. Circulating irisin levels are not correlated with BMI, age, and other biological parameters in obese and diabetic patients. Endocrine. 2014;46(3):674-7.
  12. Huh JY, Panagiotou G, Mougios V, Brinkoetter M, Vamvini MT, Schneider BE, et al. FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metabolism. 2012;61(12):1725-38.
  13. Park KH, Zaichenko L, Peter P, Davis CR, Crowell JA, Mantzoros CS. Diet quality is associated with circulating C-reactive protein but not irisin levels in humans. Metabolism. 2014;63(2):233-41.
  14. Pardo M, Crujeiras AB, Amil M, Aguera Z, Jimenez-Murcia S, Banos R, et al. Association of irisin with fat mass, resting energy expenditure, and daily activity in conditions of extreme body mass index. Int J Endocrinol. 2014;2014:857270.
  15. Crujeiras AB, Zulet MA, Lopez-Legarrea P, de la Iglesia R, Pardo M, Carreira MC, et al. Association between circulating irisin levels and the promotion of insulin resistance during the weight maintenance period after a dietary weight-lowering program in obese patients. Metabolism. 2014;63(4):520-31.
  16. Barja-Fernandez S, Folgueira C, Castelao C, Al-Massadi O, Bravo SB, Garcia-Caballero T, et al. FNDC5 is produced in the stomach and associated to body composition. Sci Rep. 2016;6:23067.
  17. Huh JY, Mougios V, Kabasakalis A, Fatouros I, Siopi A, Douroudos, II, et al. Exercise-induced irisin secretion is independent of age or fitness level and increased irisin may directly modulate muscle metabolism through AMPK activation. J Clin Endocrinol Metab. 2014;99(11):e2154-61.
  18. Crujeiras AB, Pardo M, Casanueva FF. Irisin: 'fat' or artefact. Clin Endocrinol (Oxf). 2015;82(4):467-74.
  19. Huerta AE, Prieto-Hontoria PL, Fernandez-Galilea M, Sainz N, Cuervo M, Martinez JA, et al. Circulating irisin and glucose metabolism in overweight/obese women: effects of alpha-lipoic acid and eicosapentaenoic acid. J Physiol Biochem. 2015;71(3):547-58.
  20. Schlogl M, Piaggi P, Votruba SB, Walter M, Krakoff J, Thearle MS. Increased 24-hour ad libitum food intake is associated with lower plasma irisin concentrations the following morning in adult humans. Appetite. 2015;90:154-9.
  21. Stengel A, Hofmann T, Goebel-Stengel M, Elbelt U, Kobelt P, Klapp BF. Circulating levels of irisin in patients with anorexia nervosa and different stages of obesity-correlation with body mass index. Peptides. 2013;39:125-30.
  22. Bagnol D, Al-Shamma HA, Behan D, Whelan K, Grottick AJ. Diet-induced models of obesity (DIO) in rodents. Curr Protoc Neurosci. 2012;Chapter 9:Unit 9. 38. 1-13.
  23. Powers SK, Criswell D, Lawler J, Martin D, Lieu FK, Ji LL, et al. Rigorous exercise training increases superoxide dismutase activity in ventricular myocardium. Am J Physiol. 1993;265(6 Pt 2):H2094-8.
  24. Bargut TC, Silva-e-Silva AC, Souza-Mello V, Mandarim-de-Lacerda CA, Aguila MB. Mice fed fish oil diet and upregulation of brown adipose tissue thermogenic markers. Eur J Nutr. 2016;55(1):159-69.
  25. Meakin PJ, Harper AJ, Hamilton DL, Gallagher J, McNeilly AD, Burgess LA, et al. Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice. Biochem J. 2012;441(1):285-96.
  26. Dali-Youcef N, Mataki C, Coste A, Messaddeq N, Giroud S, Blanc S, et al. Adipose tissue-specific inactivation of the retinoblastoma protein protects against diabesity because of increased energy expenditure. Proc Natl Acad Sci U S A. 2007;104(25):10703-8.
  27. Sesti G, Andreozzi F, Fiorentino TV, Mannino GC, Sciacqua A, Marini MA, et al. High circulating irisin levels are associated with insulin resistance and vascular atherosclerosis in a cohort of nondiabetic adult subjects. Acta Diabetol. 2014;51(5):705-13.
  28. Al-Daghri NM, Alkharfy KM, Rahman S, Amer OE, Vinodson B, Sabico S, et al. Irisin as a predictor of glucose metabolism in children: sexually dimorphic effects. Eur J Clin Invest. 2014;44(2):119-24.
  29. Brenmoehl J, Albrecht E, Komolka K, Schering L, Langhammer M, Hoeflich A, et al. Irisin is elevated in skeletal muscle and serum of mice immediately after acute exercise. Int J Biol Sci. 2014;10(3):338-49.
  30. Guilford BL, Parson JC, Grote CW, Vick SN, Ryals JM, Wright DE. Increased FNDC5 is associated with insulin resistance in high fat-fed mice. Physiol Rep. 2017;5(13). 1-10.
  31. Keuper M, Jastroch M, Yi CX, Fischer-Posovszky P, Wabitsch M, Tschop MH, et al. Spare mitochondrial respiratory capacity permits human adipocytes to maintain ATP homeostasis under hypoglycemic conditions. FASEB J. 2014;28(2):761-70.
  32. Roca-Rivada A, Castelao C, Senin LL, Landrove MO, Baltar J, Belen Crujeiras A, et al. FNDC5/irisin is not only a myokine but also an adipokine. PLoS One. 2013;8(4): e60563.
  33. Kraemer RR, Shockett P, Webb ND, Shah U, Castracane VD. A transient elevated irisin blood concentration in response to prolonged, moderate aerobic exercise in young men and women. Horm Metab Res. 2014;46(2):150-4.
  34. Pekkala S, Wiklund PK, Hulmi JJ, Ahtiainen JP, Horttanainen M, Pollanen E, et al. Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health? J Physiol. 2013;591(21):5393-400.
  35. Timmons JA, Baar K, Davidsen PK, Atherton PJ. Is irisin a human exercise gene? Nature. 2012;488(7413):E9-10; discussion E-1.
  36. Choi YK, Kim MK, Bae KH, Seo HA, Jeong JY, Lee WK, et al. Serum irisin levels in new-onset type 2 diabetes. Diabetes Res Clin Pract. 2013;100(1):96-101.
  37. Sparks LM, Xie H, Koza RA, Mynatt R, Hulver MW, Bray GA, et al. A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle. Diabetes. 2005;54(7):1926-33.
  38. Crunkhorn S, Dearie F, Mantzoros C, Gami H, da Silva WS, Espinoza D, et al. Peroxisome proliferator activator receptor gamma coactivator-1 expression is reduced in obesity: potential pathogenic role of saturated fatty acids and p38 mitogen-activated protein kinase activation. J Biol Chem. 2007;282(21):15439-50.
Sport Physiology
Volume 11, Issue 41
April 2019
Pages 63-80

  • Receive Date 08 June 2017
  • Revise Date 26 August 2017
  • Accept Date 17 September 2017