The Effect of High Intensity Interval training and Moderate Intensity Continuous Training on Mitochondrial Content and PGC-1α of Subcutaneous Adipose Tissue in Male Rats with High Fat Diet Induced Obesity

Document Type : Research Paper


1 PhD Student, Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Guilan, Rasht, Iran

2 Professor, Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Guilan, Rasht, Iran

3 Assistant Professor, Neuroscience Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran


The aim of this study was to investigate the effects of high intensity interval training (HIIT) and moderate intensity continuous training (MICT) on mitochondrial content and PGC-1α of subcutaneous adipose tissue in obese male rats. 40 male rats after inducing obesity with high fat diet (for 10 weeks), 8 rats from the high-fat diet group (O) and 8 rats of the standard diet group (C) were sacrificed and other obese rats were randomly divided into 3 groups: obesity control (OC), moderate intensity continuous training (MICT) and high intensity interval training (HIIT). The HIIT protocol included 10 bouts of 4-min. activity with the intensity equivalent to 85-90% vo2max and 2-min. active rest intervals. MICT protocol was carried out with the intensity of 65-70% VO2max with a covered distance similar to HIIT protocol for 12 weeks and 5 sessions per week. Western Blot method was used to measure PGC-1α and RT-PCR method was applied to measure mtDNA gene expression. Data were analyzed using ANOVA, ANCOVA and Bonferroni tests. The level of significance was considered as P≤0.05. The results of data analysis showed that HIIT and MICT drastically increased protein contents of PGC-1α and mtDNA expression (P<0.05). However, HIIT had more effects (P<0.05). Generally, it seems that HIIT and MICT increase mitochondrial biogenesis in subcutaneous adipose tissue while the effects of HIIT are drastically higher.


1.   Pedersen BK, Saltin B. Exercise as medicine–evidence for prescribing exercise as therapy in 26 different chronic diseases. Scandinavian journal of medicine & science in sports. 2015;25(S3):1-72.
2.   Madamanchi NR, Runge MS. Mitochondrial dysfunction in atherosclerosis. Circulation research. 2007;100(4):460-73.
3.   Schiff M, Loublier S, Coulibaly A, Benit P, De Baulny HO, Rustin P. Mitochondria and diabetes mellitus: untangling a conflictive relationship? Journal of inherited metabolic disease. 2009;32(6):684-98.
4.   Ukropcova B, Sereda O, De Jonge L, Bogacka I, Nguyen T, Xie H, et al. Family history of diabetes links impaired substrate switching and reduced mitochondrial content in skeletal muscle. Diabetes. 2007;56(3):720-7.
5.   Cummins TD, Holden CR, Sansbury BE, Gibb AA, Shah J, Zafar N, et al. Metabolic remodeling of white adipose tissue in obesity. American Journal of Physiology-Endocrinology and Metabolism. 2014;307(3):E262-E77.
6.   Laye MJ, Rector RS, Warner SO, Naples SP, Perretta AL, Uptergrove GM, et al. Changes in visceral adipose tissue mitochondrial content with type 2 diabetes and daily voluntary wheel running in OLETF rats. The Journal of physiology. 2009;587(14):3729-39.
7.   Heinonen S, Buzkova J, Muniandy M, Kaksonen R, Ollikainen M, Ismail K, et al. Impaired mitochondrial biogenesis in adipose tissue in acquired obesity.Diabetes. 2015:db141937.
8.   Dahlman I, Forsgren M, Sjögren A, Nordström EA, Kaaman M, Näslund E, et al. Downregulation of electron transport chain genes in visceral adipose tissue in type 2 diabetes independent of obesity and possibly involving tumor necrosis factor-α. Diabetes. 2006;55(6):1792-9.
9.   Trevellin E, Scorzeto M, Olivieri M, Granzotto M, Valerio A, Tedesco L, et al. Exercise training induces mitochondrial biogenesis and glucose uptake in subcutaneous adipose tissue through eNOS-dependent mechanisms. Diabetes. 2014;63(8):2800-11.
10. Sutherland LN, Bomhof MR, Capozzi LC, Basaraba SA, Wright DC. Exercise and adrenaline increase PGC‐1α mRNA expression in rat adipose tissue. The Journal of physiology. 2009;587(7):1607-17.
11. Larsen S, Danielsen J, Søndergård SD, Søgaard D, Vigelsoe A, Dybboe R, et al. The effect of high‐intensity training on mitochondrial fat oxidation in skeletal muscle and subcutaneous adipose tissue. Scandinavian journal of medicine & science in sports. 2015;25(1).
12. Chomentowski P, Coen PM, Radiková Z, Goodpaster BH, Toledo FG. Skeletal muscle mitochondria in insulin resistance: differences in intermyofibrillar versus subsarcolemmal subpopulations and relationship to metabolic flexibility. The Journal of Clinical Endocrinology & Metabolism. 2011;96(2):494-503.
13. Beaudoin M-S, Snook LA, Arkell AM, Simpson JA, Holloway GP, Wright DC. Resveratrol supplementation improves white adipose tissue function in a depot-specific manner in Zucker diabetic fatty rats. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2013;305(5):R542-R51.
14. Vega RB, Huss JM, Kelly DP. The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor α in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Molecular and cellular biology. 2000;20(5):1868-76.
15. Wu H, Kanatous SB, Thurmond FA, Gallardo T, Isotani E, Bassel-Duby R, et al. Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science. 2002;296(5566):349-52.
16. Hock MB, Kralli A. Transcriptional control of mitochondrial biogenesis and function. Annual review of physiology. 2009;71:177-203.
17. Baar K. Nutrition and the adaptation to endurance training. Sports Medicine. 2014;44(1):5-12.
18. Kang C, Li Ji L. Role of PGC‐1α signaling in skeletal muscle health and disease. Annals of the New York Academy of Sciences. 2012;1271(1):110-7.
19. Little JP, Safdar A, Bishop D, Tarnopolsky MA, Gibala MJ. An acute bout of high-intensity interval training increases the nuclear abundance of PGC-1α and activates mitochondrial biogenesis in human skeletal muscle. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2011;300(6):R1303-R10.
20. Hoshino D, Yoshida Y, Kitaoka Y, Hatta H, Bonen A. High-intensity interval training increases intrinsic rates of mitochondrial fatty acid oxidation in rat red and white skeletal muscle. Applied Physiology, Nutrition, and Metabolism. 2013;38(3):326-33.
21. Granata C, Oliveira RS, Little JP, Renner K, Bishop DJ. Training intensity modulates changes in PGC-1α and p53 protein content and mitochondrial respiration, but not markers of mitochondrial content in human skeletal muscle. The FASEB Journal. 2015;30(2):959-70.
22. Cochran AJ, Percival ME, Tricarico S, Little JP, Cermak N, Gillen JB, et al. Intermittent and continuous high‐intensity exercise training induce similar acute but different chronic muscle adaptations. Experimental physiology. 2014;99(5):782-91.
23. Burgomaster KA, Howarth KR, Phillips SM, Rakobowchuk M, MacDonald MJ, McGee SL, et al. Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans. The Journal of physiology. 2008;586(1):151-60.
24. Gibala MJ, McGee SL. Metabolic adaptations to short-term high-intensity interval training: a little pain for a lot of gain? Exercise and sport sciences reviews. 2008;36(2):58-63.
25. Evans CC, LePard KJ, Kwak JW, Stancukas MC, Laskowski S, Dougherty J, et al. Exercise prevents weight gain and alters the gut microbiota in a mouse model of high fat diet-induced obesity. PloS one. 2014;9(3):e92193.
26. Hafstad AD, Lund J, Hadler-Olsen E, Höper AC, Larsen TS, Aasum E. High-and moderate-intensity training normalizes ventricular function and mechanoenergetics in mice with diet-induced obesity. Diabetes. 2013;62(7):2287-94.
27. Matthews D, Hosker J, Rudenski A, Naylor B, Treacher D, Turner R. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-9.
28. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell. 1999;98(1):115-24.
29. Sutherland LN, Capozzi LC, Turchinsky NJ, Bell RC, Wright DC. Time course of high-fat diet-induced reductions in adipose tissue mitochondrial proteins: potential mechanisms and the relationship to glucose intolerance. American journal of physiology-endocrinology and metabolism. 2008;295(5):E1076-E83.
30. Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463.
31. Gibala MJ, McGee SL, Garnham AP, Howlett KF, Snow RJ, Hargreaves M. Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1α in human skeletal muscle. Journal of applied physiology. 2009;106(3):929-34.
32. Cantó C, Auwerx J. PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Current opinion in lipidology. 2009;20(2):98.
33. Qiang L, Wang L, Kon N, Zhao W, Lee S, Zhang Y, et al. Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Pparγ. Cell. 2012;150(3):620-32.
34. Bartlett JD, Hwa Joo C, Jeong T-S, Louhelainen J, Cochran AJ, Gibala MJ, et al. Matched work high-intensity interval and continuous running induce similar increases in PGC-1α mRNA, AMPK, p38, and p53 phosphorylation in huma skeletal muscle. Journal of applied physiology. 2012;112(7):1135-43.
35. Huang C-C, Wang T, Tung Y-T, Lin W-T. Effect of exercise training on skeletal muscle SIRT1 and PGC-1α expression levels in rats of different age. International journal of medical sciences. 2016;13(4):260.
36. Yan M, Audet-Walsh É, Manteghi S, Dufour CR, Walker B, Baba M, et al. Chronic AMPK activation via loss of FLCN induces functional beige adipose tissue through PGC-1α/ERRα. Genes & development. 2016;30(9):1034-46.
37. Andrade JMO, Frade ACM, Guimarães JB, Freitas KM, Lopes MTP, Guimarães ALS, et al. Resveratrol increases brown adipose tissue thermogenesis markers by increasing SIRT1 and energy expenditure and decreasing fat accumulation in adipose tissue of mice fed a standard diet. European journal of nutrition. 2014;53(7):1503-10.
38. Cantó C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature. 2009;458(7241):1056.
39. Egan B, Carson BP, Garcia‐Roves PM, Chibalin AV, Sarsfield FM, Barron N, et al. Exercise intensity‐dependent regulation of peroxisome proliferator‐activated receptor γ coactivator‐1α mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle. The Journal of physiology. 2010;588(10):1779-90.
40. Saleem A, Adhihetty PJ, Hood DA. Role of p53 in mitochondrial biogenesis and apoptosis in skeletal muscle. Physiological genomics. 2009;37(1):58-66.
41. Choe SS, Huh JY, Hwang IJ, Kim JI, Kim JB. Adipose tissue remodeling: its role in energy metabolism and metabolic disorders. Frontiers in endocrinology. 2016;7:30.
42. Lundgren M, Svensson M, Lindmark S, Renström F, Ruge T, Eriksson JW. Fat cell enlargement is an independent marker of insulin resistance and ‘hyperleptinaemia’. Diabetologia. 2007;50(3):625-33.
43. Gollisch KS, Brandauer J, Jessen N, Toyoda T, Nayer A, Hirshman MF, et al. Effects of exercise training on subcutaneous and visceral adipose tissue in normal-and high-fat diet-fed rats. American Journal of Physiology-Endocrinology and Metabolism. 2009;297(2):E495-E504.
44. Heilbronn LK, Campbell LV. Adipose tissue macrophages, low grade inflammation and insulin resistance in human obesity. Current pharmaceutical design. 2008;14(12):1225-30.
45. Iellamo F, Caminiti G, Sposato B, Vitale C, Massaro M, Rosano G, et al. Effect of High-Intensity interval training versus moderate continuous training on 24-h blood pressure profile and insulin resistance in patients with chronic heart failure. Internal and emergency medicine. 2014;9(5):547-52.
46. Chavanelle V, Boisseau N, Otero YF, Combaret L, Dardevet D, Montaurier C, et al. Effects of high-intensity interval training and moderate-intensity continuous training on glycaemic control and skeletal muscle mitochondrial function in db/db mice. Scientific reports. 2017;7(1):204.
47. Motiani KK, Savolainen AM, Eskelinen J-J, Toivanen J, Ishizu T, Yli-Karjanmaa M, et al. Two weeks of moderate-intensity continuous training, but not high-intensity interval training, increases insulin-stimulated intestinal glucose uptake. Journal of Applied Physiology. 2017;122(5):1188-97.
48. Wang N, Liu Y, Ma Y, Wen D. High-intensity interval versus moderate-intensity continuous training: Superior metabolic benefits in diet-induced obesity mice. Life sciences. 2017;191:122-31.
49. Wallberg-Henriksson H, Holloszy J. Contractile activity increases glucose uptake by muscle in severely diabetic rats. Journal of Applied Physiology. 1984;57(4):1045-9.
50. Richter EA, Mikines K, Galbo H, Kiens B. Effect of exercise on insulin action in human skeletal muscle. Journal of applied physiology. 1989;66(2):876-85.
51. Bradley H, Shaw CS, Worthington PL, Shepherd SO, Cocks M, Wagenmakers AJ. Quantitative immunofluorescence microscopy of subcellular GLUT4 distribution in human skeletal muscle: effects of endurance and sprint interval training. Physiological reports. 2014;2(7):e12085.
52. Hood MS, Little JP, Tarnopolsky MA, Myslik F, Gibala MJ. Low-volume interval training improves muscle oxidative capacity in sedentary adults. Medicine and science in sports and exercise. 2011;43(10):1849-56.
53. Liang H, Ward WF. PGC-1α: a key regulator of energy metabolism. Advances in physiology education. 2006;30(4):145-51.