Int J Med Sci 2018; 15(6):628-637. doi:10.7150/ijms.22723 This issue

Research Paper

Resveratrol attenuates denervation-induced muscle atrophy due to the blockade of atrogin-1 and p62 accumulation

Yuka Asami1, Miki Aizawa1, Masakazu Kinoshita1, Junji Ishikawa3, Kunihiro Sakuma1,2✉

1. Research Center for Physical Fitness, Sports and Health, Toyohashi University of Technology, 1-1 Hibarigaoka, Tenpaku-cho, Toyohashi 441-8580, Japan
2. Institute for Liberal Arts, Environment and Society, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan
3. FANCL Research Institute, 12-13 Kamishinano, Totsuka-ku, Yokohama, 244-0806, Japan

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Asami Y, Aizawa M, Kinoshita M, Ishikawa J, Sakuma K. Resveratrol attenuates denervation-induced muscle atrophy due to the blockade of atrogin-1 and p62 accumulation. Int J Med Sci 2018; 15(6):628-637. doi:10.7150/ijms.22723. Available from

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Decrease in activity stress induces skeletal muscle atrophy. A previous study showed that treatment with resveratrol inhibits muscular atrophy in mdx mice, a model of DMD. However, almost all studies using resveratrol supplementation have only looked at adaptive changes in the muscle weight. The present study was designed to elucidate whether the resveratrol-inducing attenuation of skeletal muscle actually reflects the adaptation of muscle fibers themselves, based on the modulation of atrogin-1- or p62-dependent signaling. Mice were fed either a normal diet or 0.5% resveratrol diet. One week later, the right sciatic nerve was cut. The wet weight, mean fiber area, and amount of atrogin-1 and p62 proteins were examined in the gastrocnemius muscle at 14 days after denervation. The 0.5% resveratrol diet significantly prevented denervation-induced decreases in both the muscle weight and fiber atrophy. In addition, dietary resveratrol suppressed the denervation-induced atrogin-1 and p62 immunoreactivity. In contrast, 0.5% resveratrol supplementation did not significantly modulate the total protein amount of atrogin-1 or p62 in the denervated muscle of mice. Resveratrol supplementation significantly prevents muscle atrophy after denervation in mice, possibly due to the decrease in atrogin-1 and p62-dependent signaling.

Keywords: resveratrol, muscle atrophy, supplementation, atrogin-1, p62, denervation