The Korean Journal of Physiology and Pharmacology

  • 제28권6호
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  • Pages.515-526
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  • 2024
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  • 1226-4512(pISSN)
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  • 2093-3827(eISSN)
대한약리학회 (The Korean Society of Pharmacology)
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Exercise improves muscle mitochondrial dysfunction-associated lipid profile under circadian rhythm disturbance

  • Yu Gu (Department of Sports Science, College of Natural Science, Jeonbuk National University) ;
  • Dong-Hun Seong (Department of Sports Science, College of Natural Science, Jeonbuk National University) ;
  • Wenduo Liu (Department of Sports Science, College of Natural Science, Jeonbuk National University) ;
  • Zilin Wang (Department of Sports Science, College of Natural Science, Jeonbuk National University) ;
  • Yong Whi Jeong (Department of Medical Informatics and Biostatistics, Graduate School, Yonsei University) ;
  • Jae-Cheol Kim (Department of Sports Science, College of Natural Science, Jeonbuk National University) ;
  • Dae Ryong Kang (Department of Precision Medicine, Yonsei University Wonju College of Medicine) ;
  • Rose Ji Eun Lee (Department of Medicine, Yonsei University Wonju College of Medicine) ;
  • Jin-Ho Koh (Department of Convergence Medicine, Yonsei University Wonju College of Medicine) ;
  • Sang Hyun Kim (Department of Sports Science, College of Natural Science, Jeonbuk National University)
  • 투고 : 2024.03.24
  • 심사 : 2024.06.05
  • 발행 : 2024.11.01
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초록

We investigated whether endurance exercise training (EXT) ameliorates circadian rhythm (CR)-induced risk factors by improving skeletal muscle (SKM) mitochondrial biogenesis, reducing oxidative stress, and modulating apoptotic protein expression. We distinguished between regular and shift workers using the National Health and Nutrition Examination Survey (NHANES) and investigated the health problems caused by shift work (CR disturbance) and the potential therapeutic effects of exercise. In our animal study, 36 rats underwent 12 weeks of CR disturbance, divided into regular and irregular CR groups. These groups were further split into EXT (n = 12) and sedentary (n = 12) for an additional 8 weeks. We analyzed SKM tissue to understand the molecular changes induced by CR and EXT. NHANES data were analyzed using SAS 9.4 and Prism 8 software, while experimental animal data were analyzed using Prism 8 software. The statistical procedures used in each experiment are indicated in the figure legends. Our studies showed that CR disturbance increases dyslipidemia, alters circadian clock proteins (BMAL1, PER2), raises apoptotic protein levels, and reduces mitochondrial biogenesis in SKM. EXT improved LDL-C and HDL-C levels without affecting muscle BMAL1 expression. It also enhanced mitochondrial biogenesis (AMPK, PGC-1α, Tfam, NADH-UO, COX-I), antioxidant levels (Catalase, SOD1, SOD2), and apoptotic protein (p53, Bax/Bcl2) expression or activity in SKM. We demonstrated that shift work-induced CR disturbance leads to dyslipidemia, diminished mitochondrial biogenesis, and reduced antioxidant capacity in SKM. However, EXT can counteract dyslipidemia under CR disturbance, potentially lowering the risk of cardiovascular disorders.

키워드

과제정보

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2022R1A2C1010080). Funding was also provided through the National Research Foundation of Korea NRF2022R1A2C1010188. This paper was supported by research funds of Jeonbuk National University in 2022.

참고문헌

  1. Reddy S, Reddy V, Sharma S. Physiology, circadian rhythm. StatPearls; 2023.
  2. Wong SD, Wright KP Jr, Spencer RL, Vetter C, Hicks LM, Jenni OG, LeBourgeois MK. Development of the circadian system in early life: maternal and environmental factors. J Physiol Anthropol. 2022;41:22.
  3. Chellappa SL, Vujovic N, Williams JS, Scheer FAJL. Impact of circadian disruption on cardiovascular function and disease. Trends Endocrinol Metab. 2019;30:767-779.
  4. Baskin KK, Winders BR, Olson EN. Muscle as a "mediator" of systemic metabolism. Cell Metab. 2015;21:237-248.
  5. Ebert SM, Al-Zougbi A, Bodine SC, Adams CM. Skeletal muscle atrophy: discovery of mechanisms and potential therapies. Physiology (Bethesda). 2019;34:232-239.
  6. Kimura K, Morisasa M, Mizushige T, Karasawa R, Kanamaru C, Kabuyama Y, Hayasaka T, Mori T, Goto-Inoue N. Lipid dynamics due to muscle atrophy induced by immobilization. J Oleo Sci. 2021;70:937-946.
  7. Hedayatnia M, Asadi Z, Zare-Feyzabadi R, Yaghooti-Khorasani M, Ghazizadeh H, Ghaffarian-Zirak R, Nosrati-Tirkani A, Mohammadi-Bajgiran M, Rohban M, Sadabadi F, Rahimi HR, Ghalandari M, Ghaffari MS, Yousefi A, Pouresmaeili E, Besharatlou MR, Moohebati M, Ferns GA, Esmaily H, Ghayour-Mobarhan M. Dyslipidemia and cardiovascular disease risk among the MASHAD study population. Lipids Health Dis. 2020;19:42.
  8. Opoku S, Gan Y, Fu W, Chen D, Addo-Yobo E, Trofimovitch D, Yue W, Yan F, Wang Z, Lu Z. Prevalence and risk factors for dyslipidemia among adults in rural and urban China: findings from the China National Stroke Screening and prevention project (CNSSPP). BMC Public Health. 2019;19:1500.
  9. Lee JH, Lee HS, Cho AR, Lee YJ, Kwon YJ. Relationship between muscle mass index and LDL cholesterol target levels: analysis of two studies of the Korean population. Atherosclerosis. 2021;325:1-7.
  10. Andrews JL, Zhang X, McCarthy JJ, McDearmon EL, Hornberger TA, Russell B, Campbell KS, Arbogast S, Reid MB, Walker JR, Hogenesch JB, Takahashi JS, Esser KA. CLOCK and BMAL1 regulate MyoD and are necessary for maintenance of skeletal muscle phenotype and function. Proc Natl Acad Sci U S A. 2010;107:19090-19095.
  11. Peek CB, Levine DC, Cedernaes J, Taguchi A, Kobayashi Y, Tsai SJ, Bonar NA, McNulty MR, Ramsey KM, Bass J. Circadian clock interaction with HIF1α mediates oxygenic metabolism and anaerobic glycolysis in skeletal muscle. Cell Metab. 2017;25:86-92.
  12. Saner NJ, Bishop DJ, Bartlett JD. Is exercise a viable therapeutic intervention to mitigate mitochondrial dysfunction and insulin resistance induced by sleep loss? Sleep Med Rev. 2018;37:60-68.
  13. Wolff G, Esser KA. Scheduled exercise phase shifts the circadian clock in skeletal muscle. Med Sci Sports Exerc. 2012;44:1663-1670.
  14. Jung CH, Son JW, Kang S, Kim WJ, Kim HS, Kim HS, Seo M, Shin HJ, Lee SS, Jeong SJ, Cho Y, Han SJ, Jang HM, Rho M, Lee S, Koo M, Yoo B, Moon JW, Lee HY, Yun JS, et al. Diabetes fact sheets in Korea, 2020: an appraisal of current status. Diabetes Metab J. 2021;45:1-10.
  15. Oh SW. Obesity and metabolic syndrome in Korea. Diabetes Metab J. 2011;35:561-566.
  16. Sun Z, Li L, Yan Z, Zhang L, Zang G, Qian Y, Wang Z. Circadian rhythm disorders elevate macrophages cytokines release and promote multiple tissues/organs dysfunction in mice. Physiol Behav. 2022;249:113772.
  17. Qin F, Dong Y, Wang S, Xu M, Wang Z, Qu C, Yang Y, Zhao J. Maximum oxygen consumption and quantification of exercise intensity in untrained male Wistar rats. Sci Rep. 2020;10:11520.
  18. Kim JC, Kang YS, Noh EB, Seo BW, Seo DY, Park GD, Kim SH. Concurrent treatment with ursolic acid and low-intensity treadmill exercise improves muscle atrophy and related outcomes in rats. Korean J Physiol Pharmacol. 2018;22:427-436.
  19. Cochran WG, Rubin DB. Controlling bias in observational studies: A review. Sankhya: The Indian Journal of Statistics, Series A. 1973;35:417-446.
  20. Sartori R, Romanello V, Sandri M. Mechanisms of muscle atrophy and hypertrophy: implications in health and disease. Nat Commun. 2021;12:330.
  21. Shimba S, Ishii N, Ohta Y, Ohno T, Watabe Y, Hayashi M, Wada T, Aoyagi T, Tezuka M. Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis. Proc Natl Acad Sci U S A. 2005;102:12071-12076.
  22. Takahashi JS. Transcriptional architecture of the mammalian circadian clock. Nat Rev Genet. 2017;18:164-179.
  23. Duong HA, Robles MS, Knutti D, Weitz CJ. A molecular mechanism for circadian clock negative feedback. Science. 2011;332:1436-1439.
  24. Wilkins AK, Barton PI, Tidor B. The Per2 negative feedback loop sets the period in the mammalian circadian clock mechanism. PLoS Comput Biol. 2007;3:e242.
  25. Wada T, Ichihashi Y, Suzuki E, Kosuge Y, Ishige K, Uchiyama T, Makishima M, Nakao R, Oishi K, Shimba S. Deletion of Bmal1 prevents diet-induced ectopic fat accumulation by controlling oxidative capacity in the skeletal muscle. Int J Mol Sci. 2018;19:2813.
  26. Lian D, Chen MM, Wu H, Deng S, Hu X. The role of oxidative stress in skeletal muscle myogenesis and muscle disease. Antioxidants (Basel). 2022;11:755.
  27. Levine AJ, Oren M. The first 30 years of p53: growing ever more complex. Nat Rev Cancer. 2009;9:749-758.
  28. Moll UM, Petrenko O. The MDM2-p53 interaction. Mol Cancer Res. 2003;1:1001-1008.
  29. Letai AG. Diagnosing and exploiting cancer's addiction to blocks in apoptosis. Nat Rev Cancer. 2008;8:121-132.
  30. Shimba S, Ogawa T, Hitosugi S, Ichihashi Y, Nakadaira Y, Kobayashi M, Tezuka M, Kosuge Y, Ishige K, Ito Y, Komiyama K, Okamatsu-Ogura Y, Kimura K, Saito M. Deficient of a clock gene, brain and muscle Arnt-like protein-1 (BMAL1), induces dyslipidemia and ectopic fat formation. PLoS One. 2011;6:e25231.
  31. Bhatti JS, Bhatti GK, Reddy PH. Mitochondrial dysfunction and oxidative stress in metabolic disorders - A step towards mitochondria based therapeutic strategies. Biochim Biophys Acta Mol Basis Dis. 2017;1863:1066-1077.
  32. Shintaku J, Peterson JM, Talbert EE, Gu JM, Ladner KJ, Williams DR, Mousavi K, Wang R, Sartorelli V, Guttridge DC. MyoD regulates skeletal muscle oxidative metabolism cooperatively with alternative NF-κB. Cell Rep. 2016;17:514-526.
  33. Jeukendrup AE. Regulation of fat metabolism in skeletal muscle. Ann N Y Acad Sci. 2002;967:217-235.
  34. Watt MJ, Hoy AJ. Lipid metabolism in skeletal muscle: generation of adaptive and maladaptive intracellular signals for cellular function. Am J Physiol Endocrinol Metab. 2012;302:E1315-E1328.
  35. Seip RL, Angelopoulos TJ, Semenkovich CF. Exercise induces human lipoprotein lipase gene expression in skeletal muscle but not adipose tissue. Am J Physiol. 1995;268:E229-E236.
  36. Lehti M, Donelan E, Abplanalp W, Al-Massadi O, Habegger KM, Weber J, Ress C, Mansfeld J, Somvanshi S, Trivedi C, Keuper M, Ograjsek T, Striese C, Cucuruz S, Pfluger PT, Krishna R, Gordon SM, Silva RA, Luquet S, Castel J, et al. High-density lipoprotein maintains skeletal muscle function by modulating cellular respiration in mice. Circulation. 2013;128:2364-2371.
  37. Jezek J, Cooper KF, Strich R. Reactive oxygen species and mitochondrial dynamics: the Yin and Yang of mitochondrial dysfunction and cancer progression. Antioxidants (Basel). 2018;7:13.
  38. Geyfman M, Kumar V, Liu Q, Ruiz R, Gordon W, Espitia F, Cam E, Millar SE, Smyth P, Ihler A, Takahashi JS, Andersen B. Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis. Proc Natl Acad Sci U S A. 2012;109:11758-11763.
  39. Wu X, Bayle JH, Olson D, Levine AJ. The p53-mdm-2 autoregulatory feedback loop. Genes Dev. 1993;7:1126-1132.
  40. Lindqvist LM, Heinlein M, Huang DC, Vaux DL. Prosurvival Bcl-2 family members affect autophagy only indirectly, by inhibiting Bax and Bak. Proc Natl Acad Sci U S A. 2014;111:8512-8517.
  41. Sestili P, Barbieri E, Martinelli C, Battistelli M, Guescini M, Vallorani L, Casadei L, D'Emilio A, Falcieri E, Piccoli G, Agostini D, Annibalini G, Paolillo M, Gioacchini AM, Stocchi V. Creatine supplementation prevents the inhibition of myogenic differentiation in oxidatively injured C2C12 murine myoblasts. Mol Nutr Food Res. 2009;53:1187-1204.
  42. Higashida K, Kim SH, Jung SR, Asaka M, Holloszy JO, Han DH. Effects of resveratrol and SIRT1 on PGC-1α activity and mitochondrial biogenesis: a reevaluation. PLoS Biol. 2013;11:e1001603. Erratum in: PLoS Biol. 2014;12:10.1371/annotation/900c9397-eeb9-4d4e-9a05-ff18d657be79.
  43. Gomes MJ, Martinez PF, Pagan LU, Damatto RL, Cezar MDM, Lima ARR, Okoshi K, Okoshi MP. Skeletal muscle aging: influence of oxidative stress and physical exercise. Oncotarget. 2017;8:20428-20440.