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A novel voluntary weightlifting model in mice promotes muscle adaptation and insulin sensitivity with simultaneous enhancement of autophagy and mTOR pathway
Author(s) -
Cui Di,
Drake Joshua C.,
Wilson Rebecca J.,
Shute Robert J.,
Lewellen Bevan,
Zhang Mei,
Zhao Henan,
Sabik Olivia L.,
Onengut Suna,
Berr Stuart S.,
Rich Stephen S.,
Farber Charles R.,
Yan Zhen
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201903055r
Subject(s) - skeletal muscle , autophagy , insulin resistance , pi3k/akt/mtor pathway , mitochondrial biogenesis , plantaris muscle , medicine , endocrinology , squat , biology , downregulation and upregulation , insulin , microbiology and biotechnology , gene , soleus muscle , signal transduction , mitochondrion , apoptosis , biochemistry , physiology
Our understanding of the molecular mechanisms underlying adaptations to resistance exercise remains elusive despite the significant biological and clinical relevance. We developed a novel voluntary mouse weightlifting model, which elicits squat‐like activities against adjustable load during feeding, to investigate the resistance exercise‐induced contractile and metabolic adaptations. RNAseq analysis revealed that a single bout of weightlifting induced significant transcriptome responses of genes that function in posttranslational modification, metabolism, and muscle differentiation in recruited skeletal muscles, which were confirmed by increased expression of fibroblast growth factor‐inducible 14 ( Fn14) , Down syndrome critical region 1 (Dscr1) and Nuclear receptor subfamily 4, group A, member 3 (Nr4a3) genes. Long‐term (8 weeks) voluntary weightlifting training resulted in significantly increases of muscle mass, protein synthesis (puromycin incorporation in SUnSET assay) and mTOR pathway protein expression (raptor, 4e‐bp‐1, and p70S6K proteins) along with enhanced muscle power (specific torque and contraction speed), but not endurance capacity, mitochondrial biogenesis, and fiber type transformation. Importantly, weightlifting training profound improved whole‐body glucose clearance and skeletal muscle insulin sensitivity along with enhanced autophagy (increased LC3 and LC3‐II/I ratio, and decreased p62/Sqstm1). These data suggest that resistance training in mice promotes muscle adaptation and insulin sensitivity with simultaneous enhancement of autophagy and mTOR pathway.