Skeletal muscle-specific Keap1 disruption modulates fatty acid utilization and enhances exercise capacity in female mice

Redox Biology

Yoshihiro Izumi¹  Nao Ohta²  Sisca Meida Wati²  Daisuke Matsumaru²  Nozomi Hatanaka²  Takahiro Onoki²  Fumiki Katsuoka³  Mitsuharu Okutsu³  Hozumi Motohashi⁴  Makoto Kanzaki⁴  Yoshihiro Hagiwara⁴  Shohei Murakami⁵  Eiji Itoi⁵  Masatomo Takahashi⁵  Takeshi Bamba⁶  Yutaka Yabe⁷ 

[1] Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, 980-8575, Japan;Department of Gene Expression Regulation, IDAC, Tohoku University, Sendai, 980-8575, Japan;Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, 980-8573, Japan;Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, 980-8575, Japan;Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan;Graduate School of Biomedical Engineering, Tohoku University, Sendai, 980-8575, Japan;Graduate School of Science, Nagoya City University, Nagoya, 467-8501, Japan;

关键词: Exercise;    Skeletal muscle;    KEAP1-NRF2 system;    Fatty acid;    Beta-oxidation;   

DOI  :  

来源: DOAJ

【 摘 要 】

Skeletal muscle health is important for the prevention of various age-related diseases. The loss of skeletal muscle mass, which is known as sarcopenia, underlies physical disability, poor quality of life and chronic diseases in elderly people. The transcription factor NRF2 plays important roles in the regulation of the cellular defense against oxidative stress, as well as the metabolism and mitochondrial activity. To determine the contribution of skeletal muscle NRF2 to exercise capacity, we conducted skeletal muscle-specific inhibition of KEAP1, which is a negative regulator of NRF2, and examined the cell-autonomous and non-cell-autonomous effects of NRF2 pathway activation in skeletal muscles. We found that NRF2 activation in skeletal muscles increased slow oxidative muscle fiber type and improved exercise endurance capacity in female mice. We also observed that female mice with NRF2 pathway activation in their skeletal muscles exhibited enhanced exercise-induced mobilization and β-oxidation of fatty acids. These results indicate that NRF2 activation in skeletal muscles promotes communication with adipose tissues via humoral and/or neuronal signaling and facilitates the utilization of fatty acids as an energy source, resulting in increased mitochondrial activity and efficient energy production during exercise, which leads to improved exercise endurance.

【 授权许可】

Unknown