High-intensity endurance exercise inhibits mitochondrial biogenesis in the skeletal muscle

doi:10.3969/j.issn.2095-4344.2015.46.008

Abstract

Abstract:

BACKGROUND: There are many reports on the effects of low-to-moderate intensity endurance exercise on mitochondrial biogenesis in the skeletal muscle, but there is no understanding about the high-intensity endurance exercise. It has not been reported whether the high-intensity endurance exercise influence the mitochondrial biogenesis in the skeletal muscle through 5′-adenosine monophosphate-activated protein kinase (AMPK)/silent information regulator factor 2 related enzyme 1 (SIRT1) signal molecules.

OBJECTIVE: To investigate the effect of AMPK/SIRT1 signaling cascade on the mitochondrial biogenesis in the skeletal muscle during different intensities of endurance exercises.

METHODS: Forty-two male Sprague-Dawley rats were randomly divided into sedentary group, moderate-intensityexercise group and high-intensity exercise group. Moderate-intensity exercise load was 28 m/min, 60 min/d; high-intensity exercise load was 38 m/min, 60 min/d. In both exercise groups, the rats had 5 days of exercise and 2 days of rest within 1 week, and the exercise lasted for totally 7 weeks. The animals of exercise groups were killed immediately, 6 hours and 24 hours after exercise. Quantitative PCR was used to detect peroxisome proliferators γ activated receptor coativator-1α (PGC-1α) and SIRT1 gene expression, and western blot to detect phosphorylated-AMPK (P-AMPK) and SIRT1 protein expression.

RESULTS AND CONCLUSION: (1) Immediately, 6 hours, 24 hours after moderate-intensity exercise, PGC-1α mRNA expression in the skeletal muscle was 362% (P < 0.01), 675% (P < 0.01) and 116% of that in the sedentary group, P-AMPK protein expression was 112%, 165% (P < 0.05), 129% (P < 0.05) of that in the sedentary group, the expressions of SIRT1 protein and mRNA were 55% (P < 0.05), 86%, 103% and 109% (P < 0.05), 155%, 132% (P < 0.05) of those in the the sedentary group, respectively. (2) Immediately, 6 hours, 24 hours after high-intensity exercise, PGC-1α mRNA expression in the skeletal muscle was 274% (P < 0.01), 130% (P < 0.05), 68% (P < 0.05) of that in the sedentary group, the expression of P-AMPK protein was 235% (P < 0.01), 166% (P < 0.05), 160% (P < 0.05) of that in the sedentary group, the expressions of SIRT1 protein and mRNA were 199% (P < 0.01), 166% (P < 0.05), 164% (P < 0.05) and 255% (P < 0.01), 292% (P < 0.01), 122% of those in the sedentary group, respectively. These findings indicate that (1) 7 weeks of moderate-intensity endurance exercise significantly increased PGC-1α gene expression in the skeletal muscle, and its mechanism may involve AMPK/SIRT1 signaling cascade; (2) 7 weeks of high-intensity endurance exercise significantly inhibited PGC-1α gene expression at 24 hours after exercise, and this process was carried out in an AMPK/SIRT1 signal cascade independent manner.
中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Mitochondria, Protein Kinases, Muscle, Skeletal

Zhang Guo-hua, Chen Shu-zhuang, Li Su-ping. High-intensity endurance exercise inhibits mitochondrial biogenesis in the skeletal muscle[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(46): 7419-7424.

Figures/Tables 5

References

[1] Geng T, Li P, Okutsu M,et al.PGC-1 plays a functional role in exercise-induced mitochondrial biogenesis and angiogenesis but not fiber-type transformation in mouse skeletal muscle.Am J Physiol Cell Physiol.2010;298(3):572-579.

[2] Uguccioni G, Hood DA. The importance of PGC-1 in contractile activity-induced mitochondrial adaptation.Am J Physiol Endocrinol Metab.2011;300(2): 361-371.

[3] Bartlett JD,Hwa Joo C,Jeong TS, et al. Matched work high-intensity interval and continuous running induce similar increases in PGC-1α mRNA, AMPK, p38, and p53 phosphorylation in human skeletal muscle. Warren GAppl Physiol.2012;112(7): 1135-1143.

[4] Frier BC, Hancock CR, Little JP,et al.Reductions in RIP140 are not required for exercise- and AICAR-mediated increases in skeletal muscle mitochondrial content.J Appl Physiol.2011; 111(3): 688-695.

[5] Steiner JL, Murphy EA, McClellan JL,et al. McClellan,et al.Exercise training increases mitochondrial biogenesis in the brain. J Appl Physiol.2011;111(4): 1066-1071.

[6] Bedford TG,Tipton CM,Wilson NC,et al.Maximum oxygen consumption of rats and its changes with various ex-perimental procedures. J Appl Physiol.1979;47(6):1278 -1283.

[7] Wisloff U,Helgerud J,Kemi OJ,et al.Intensity-con-trolled treadmill running in rats: VO2max and cardiac hy-pertrophy. Am J Physiol Heart Circ Physiol.2001;280: 1301-1310.

[8] Cassano P,Sciancalepore AG,Pesce V,et al. Acetyl-L-carnitine feeding to unloaded rats triggers in soleus muscle the coordinated expression of genes involved in mitochondrial biogenesis. Biochimica et Biophysica Acta ( BBA) Bioener -getics.2006;1757:1421-1428.

[9] Wagatsuma A,Kotake N,Kawachi T,et al. Mitochondrial adaptations in skeletal muscle to hindlimb unloading. Molecular and cellular biochemistry.2010;350(1-2):1-11.

[10] Liu J,Peng YH,Cui ZW,et al. Depressed mitochondrial biogenesis and dynamic remodeling in mouse tibialis anterior and gastrocnemius induced by 4-week hindlimb unloading. IUBMB life.2012;64(11):901-910.

[11] Wu Z,Puigserver P,Andersson U,et al.Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell.1999;98(1):115-124.

[12] Fujimoto E,Yamaguchi W,Terada S,et al.Change inPGC-1α Expression in Rat Skeletal Muscle after Low-intensity Prolonged Swimming Exercise.J Physiol Anthropol. 2011; 30(1): 23-27.

[13] Li L, Chen Y, Gibson SB.Starvation-induced autophagy is regulated by mitochondrial reactive oxygen species leading to AMPK activation. Cell Signal. 2013;25(1):50-65.

[14] Mackenzie RM, Salt IP, Miller WH,et al. Mitochondrial reactive oxygen species enhance AMP-activated protein kinase activation in the endothelium of patients with coronary artery disease and diabetes. Clin Sci (Lond).2013;124(6): 403-411.

[15] Davis JM, Murphy EA, Carmichael MD,et al.Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance.Am J Physiol Regulatory Integrative Comp Physiol.2009;296(4): 1071-1077.

[16] Canto C, Jiang LQ, Deshmukh AS,et al.Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell Metab.2010; 11(3): 213-219.

[17] Funk JA, Odejinmi S, Schnellmann RG.Schnellmann. SRT1720 induces mitochondrial biogenesis and rescues mitochondrial function after oxidant injury in renal proximal tubule cells. J Pharmacol Exp Ther.2010; 333(2): 593-601.

[18] Khalil HS, Tummala H, DeCaris L, et al.Pharmacological inhibition of ATM results in mitochondrial biogenesis in AMPK independent manner. Cancer Res. 2013; 73(4): 1697.

[19] Menzies KJ, Singh K, Saleem A, et al.Sirtuin 1-mediated effects of exercise and resveratrol on mitochondrial biogenesis. J Biol Chem.2013;288: 6968-6979.

[20] Chabi B, Adhihetty PJ, O'Leary MF, et al.Relationship between Sirt1 expression and mitochondrial proteins during conditions of chronic muscle use and disuse. J Appl Physiol. 2009;107(6): 1730-1735.

[21] Gurd BJ, Yoshida Y, McFarlan JT,et al.Nuclear SIRT1 activity, but not protein content, regulates mitochondrial biogenesis in rat and human skeletal muscle. Am J Physiol Regulatory Integrative Comp Physiol.2011; 301(1): 67-75.