Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences, Kobe, Japan.
Department of Rehabilitation, Nose Hospital, Kobe, Japan.
Physiol Rep. 2021 Mar;9(5):e14763. doi: 10.14814/phy2.14763.
The effects of malnutrition on skeletal muscle result in not only the loss of muscle mass but also fatigue intolerance. It remains unknown whether the metabolic capacity is related to the fiber type composition of skeletal muscle under malnourished condition although malnutrition resulted in preferential atrophy in fast muscle. The purpose of the present study was to investigate the effects of metabolic capacity in fast and slow muscles via the energy-sensing of AMPK and SIRT1 in malnutrition. Wistar rats were randomly divided into control and malnutrition groups. The rats in the malnutrition group were provided with a low-protein diet, and daily food intake was limited to 50% for 12 weeks. Malnutrition with hypoalbuminemia decreased the body weight and induced the loss of plantaris muscle mass, but there was little change in the soleus muscle. An increase in the superoxide level in the plasma and a decrease in SOD-2 protein expression in both muscles were observed in the malnutrition group. In addition, the expression level of AMPK in the malnutrition group increased in both muscles. Conversely, the expression level of SIRT1 decreased in both muscles of the malnutrition group. In addition, malnutrition resulted in a decrease in the expression levels of PGC-1α and PINK protein, and induced a decrease in the levels of two key mitochondrial enzymes (succinate dehydrogenase and citrate synthase) and COX IV protein expression in both muscles. These results indicate that malnutrition impaired the metabolic capacity in both fast and slow muscles via AMPK-independent SIRT1 inhibition induced by increased oxidative stress.
营养不良对骨骼肌的影响不仅导致肌肉质量的丧失，还导致对疲劳的耐受性降低。尽管营养不良导致快肌优先萎缩，但代谢能力与营养不良状态下骨骼肌的纤维类型组成是否有关仍然未知。本研究的目的是通过 AMPK 和 SIRT1 的能量感应研究营养不良时快肌和慢肌代谢能力的变化。Wistar 大鼠随机分为对照组和营养不良组。营养不良组给予低蛋白饮食，每日食物摄入量限制为正常量的 50%，持续 12 周。低蛋白血症引起的营养不良导致体重减轻，并引起比目鱼肌质量的丧失，但跖肌变化不大。营养不良组血浆中超氧化物水平升高，两种肌肉中的 SOD-2 蛋白表达减少。此外，营养不良组两种肌肉中的 AMPK 表达增加。相反，营养不良组两种肌肉中的 SIRT1 表达降低。此外，营养不良导致 PGC-1α 和 PINK 蛋白表达水平降低，并诱导两种关键线粒体酶（琥珀酸脱氢酶和柠檬酸合酶）和 COX IV 蛋白表达水平降低。这些结果表明，氧化应激增加导致 AMPK 非依赖性 SIRT1 抑制，从而损害了快肌和慢肌的代谢能力。
