Nicotinamide Phosphoribosyltransferase‐elevated NAD + biosynthesis prevents muscle disuse atrophy by reversing mitochondrial dysfunction

作者：Yao Zhang, Yingming Wang, Shuai Lu, Rui Zhong, Zhilin Liu, Qichun Zhao, Chongyang Wang · 发表于：Journal of Cachexia Sarcopenia and Muscle · 年份：2023 · DOI：10.1002/jcsm.13182 · 被引用次数：21 · 研究领域：Muscle Physiology and Disorders、Sirtuins and Resveratrol in Medicine、Exercise and Physiological Responses

Abstract Background It is well known that muscle disuse atrophy is associated with mitochondrial dysfunction, which is implicated in reduced nicotinamide adenine dinucleotide (NAD + ) levels. Nicotinamide phosphoribosyltransferase (NAMPT), a rate‐limiting enzyme in NAD + biosynthesis, may serve as a novel strategy to treat muscle disuse atrophy by reversing mitochondrial dysfunction. Methods To investigate the effects of NAMPT on the prevention of disuse atrophy of skeletal muscles predominantly composed of slow‐twitch (type I) or fast‐twitch (type II) fibres, rabbit models of rotator cuff tear‐induced supraspinatus muscle atrophy and anterior cruciate ligament (ACL) transection‐induced extensor digitorum longus (EDL) atrophy were established and then administered NAMPT therapy. Muscle mass, fibre cross‐sectional area (CSA), fibre type, fatty infiltration, western blot, and mitochondrial function were assayed to analyse the effects and molecular mechanisms of NAMPT in preventing muscle disuse atrophy. Results Acute disuse of the supraspinatus muscle exhibited significant loss of mass (8.86 ± 0.25 to 5.10 ± 0.79 g; P < 0.001) and decreased fibre CSA (3939.6 ± 136.1 to 2773.4 ± 217.6 μm 2 , P < 0.001), which were reversed by NAMPT (muscle mass 6.17 ± 0.54 g, P = 0.0033; fibre CSA, 3219.8 ± 289.4 μm 2 , P = 0.0018). Disuse‐induced impairment of mitochondrial function were significantly improved by NAMPT, including citrate synthase activity (40.8 ± 6.3 to 50.5 ± 5.6 nmol/mi...