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Original Article

Korean J Physiol Pharmacol 2024; 28(6): 515-526

Published online November 1, 2024 https://doi.org/10.4196/kjpp.2024.28.6.515

Copyright © Korean J Physiol Pharmacol.

Exercise improves muscle mitochondrial dysfunction-associated lipid profile under circadian rhythm disturbance

Yu Gu1,#, Dong-Hun Seong1,#, Wenduo Liu1, Zilin Wang1, Yong Whi Jeong2, Jae-Cheol Kim1, Dae Ryong Kang3, Rose Ji Eun Lee4, Jin-Ho Koh5,6,*, and Sang Hyun Kim1,*

1Department of Sports Science, College of Natural Science, Jeonbuk National University, Jeonju 54896, 2Department of Medical Informatics and Biostatistics, Graduate School, Yonsei University, 3Department of Precision Medicine, 4Department of Medicine, 5Department of Convergence Medicine, 6Department of Global Medical Science, Yonsei University Wonju College of Medicine, Wonju 26426, Korea

Correspondence to:Jin-Ho Koh
E-mail: jinhokoh@yonsei.ac.kr
Sang Hyun Kim
E-mail: sh5275@jbnu.ac.kr

#These authors contributed equally to this work.

Author contributions: J.H.K. and S.H.K.: Conceived and designed the experiments. Y.G., D.H.S., W.L., Z.W., and S.H.K.: Performed the experiments and analyzed the data for animal study. Y.W.J., D.R.K., J.H.K., and S.H.K.: Data analysis for human study. Y.G., D.H.S., Y.W.J., J.H.K., and S.H.K.: Data analysis and interpretation. D.R.K., J.C.K., J.H.K., and S.H.K.: Contributed reagents, materials, and analytical tools. Y.G., D.H.S., R.J.E.L., J.H.K., and S.H.K.: Drafting the manuscript. R.J.E.L., J.H.K., and S.H.K.: Edit the manuscript. All authors: Final approval of manuscript to be published.

Received: March 24, 2024; Revised: May 24, 2024; Accepted: June 5, 2024

Abstract

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 HDLC 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.

Keywords: Circadian rhythm, Exercise, Lipids, Mitochondria, Skeletal muscle