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An integrative profiling of metabolome and transcriptome in the plasma and skeletal muscle following an exercise intervention in diet-induced obese mice
Shuang Han1,2,† , Qingqian Wu1,3,† , Mengying Wang4,† , Miqi Yang1 , Chen Sun5 , Jiaqi Liang5 , Xiaozhen Guo6 , Zheyu Zhang1 , Jingya Xu1 , Xinyuan Qiu7 , Cen Xie6 , Siyu Chen2,5 , Yue Gao2,* , Zhuo-Xian Meng1,2,3,*
1Department of Pathology and Pathophysiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
2Department of Geriatrics, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
3Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China
4Department of Big Data in Health Science School of Public Health, Zhejiang University School of Medicine, Hangzhou 310003, China
5State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
6State Key Laboratory of Drug Research, Shanghai Institute of Material Medical, Chinese Academy of Sciences, Shanghai 201203, China
7Department of Biology and Chemistry, College of Liberal Arts and Sciences, National University of Defense Technology, Changsha 410073, China
These authors contributed equally to this work
*Correspondence to:Yue Gao , Zhuo-Xian Meng ,
J Mol Cell Biol, Volume 15, Issue 3, March 2023, mjad016,
Keyword: type 2 diabetes, exercise intervention, metabolomics, transcriptomics

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....