PMID- 36882217 OWN - NLM STAT- MEDLINE DCOM- 20231023 LR - 20231031 IS - 1759-4685 (Electronic) IS - 1674-2788 (Print) IS - 1759-4685 (Linking) VI - 15 IP - 3 DP - 2023 Aug 3 TI - An integrative profiling of metabolome and transcriptome in the plasma and skeletal muscle following an exercise intervention in diet-induced obese mice. LID - 10.1093/jmcb/mjad016 [doi] LID - mjad016 AB - Exercise intervention at the early stage of type 2 diabetes mellitus (T2DM) can aid in the maintenance of blood glucose homeostasis and prevent the development of macrovascular and microvascular complications. However, the exercise-regulated pathways that prevent the development of T2DM remain largely unclear. In this study, two forms of exercise intervention, treadmill training and voluntary wheel running, were conducted for high-fat diet (HFD)-induced obese mice. We observed that both forms of exercise intervention alleviated HFD-induced insulin resistance and glucose intolerance. Skeletal muscle is recognized as the primary site for postprandial glucose uptake and for responsive alteration beyond exercise training. Metabolomic profiling of the plasma and skeletal muscle in Chow, HFD, and HFD-exercise groups revealed robust alterations in metabolic pathways by exercise intervention in both cases. Overlapping analysis identified nine metabolites, including beta-alanine, leucine, valine, and tryptophan, which were reversed by exercise treatment in both the plasma and skeletal muscle. Transcriptomic analysis of gene expression profiles in the skeletal muscle revealed several key pathways involved in the beneficial effects of exercise on metabolic homeostasis. In addition, integrative transcriptomic and metabolomic analyses uncovered strong correlations between the concentrations of bioactive metabolites and the expression levels of genes involved in energy metabolism, insulin sensitivity, and immune response in the skeletal muscle. This work established two models of exercise intervention in obese mice and provided mechanistic insights into the beneficial effects of exercise intervention on systemic energy homeostasis. CI - (c) The Author(s) (2023). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS. FAU - Han, Shuang AU - Han S AD - Department of Pathology and Pathophysiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China. AD - Department of Geriatrics, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China. FAU - Wu, Qingqian AU - Wu Q AD - Department of Pathology and Pathophysiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China. AD - Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China. FAU - Wang, Mengying AU - Wang M AD - Department of Big Data in Health Science School of Public Health, Zhejiang University School of Medicine, Hangzhou 310003, China. FAU - Yang, Miqi AU - Yang M AD - Department of Pathology and Pathophysiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China. FAU - Sun, Chen AU - Sun C AD - State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China. FAU - Liang, Jiaqi AU - Liang J AD - State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China. FAU - Guo, Xiaozhen AU - Guo X AD - State Key Laboratory of Drug Research, Shanghai Institute of Material Medical, Chinese Academy of Sciences, Shanghai 201203, China. FAU - Zhang, Zheyu AU - Zhang Z AUID- ORCID: 0000-0002-7994-1297 AD - Department of Pathology and Pathophysiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China. FAU - Xu, Jingya AU - Xu J AD - Department of Pathology and Pathophysiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China. FAU - Qiu, Xinyuan AU - Qiu X AUID- ORCID: 0000-0002-9662-8075 AD - Department of Biology and Chemistry, College of Liberal Arts and Sciences, National University of Defense Technology, Changsha 410073, China. FAU - Xie, Cen AU - Xie C AD - State Key Laboratory of Drug Research, Shanghai Institute of Material Medical, Chinese Academy of Sciences, Shanghai 201203, China. FAU - Chen, Siyu AU - Chen S AD - State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China. FAU - Gao, Yue AU - Gao Y AD - Department of Geriatrics, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China. FAU - Meng, Zhuo-Xian AU - Meng ZX AD - Department of Pathology and Pathophysiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China. AD - Department of Geriatrics, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China. AD - Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Mol Cell Biol JT - Journal of molecular cell biology JID - 101503669 SB - IM MH - Mice MH - Animals MH - Humans MH - Transcriptome MH - Mice, Obese MH - *Diabetes Mellitus, Type 2/metabolism MH - Motor Activity MH - *Insulin Resistance MH - Diet, High-Fat/adverse effects MH - Metabolome MH - Muscle, Skeletal/metabolism MH - Exercise Therapy MH - Mice, Inbred C57BL PMC - PMC10576543 OTO - NOTNLM OT - exercise intervention OT - metabolomics OT - transcriptomics OT - type 2 diabetes EDAT- 2023/03/08 06:00 MHDA- 2023/10/23 00:44 PMCR- 2023/03/07 CRDT- 2023/03/07 20:53 PHST- 2022/10/10 00:00 [received] PHST- 2023/02/02 00:00 [revised] PHST- 2023/03/06 00:00 [accepted] PHST- 2023/10/23 00:44 [medline] PHST- 2023/03/08 06:00 [pubmed] PHST- 2023/03/07 20:53 [entrez] PHST- 2023/03/07 00:00 [pmc-release] AID - 7071897 [pii] AID - mjad016 [pii] AID - 10.1093/jmcb/mjad016 [doi] PST - ppublish SO - J Mol Cell Biol. 2023 Aug 3;15(3):mjad016. doi: 10.1093/jmcb/mjad016.