Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China; College of Food Science & Nutritional Engineering, China Agricultural University, Beijing, China.
Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization (Southwest Minzu University), Ministry of Education, Chengdu, China.
J Nutr Biochem. 2021 Dec;98:108804. doi: 10.1016/j.jnutbio.2021.108804. Epub 2021 Jun 24.
Obesity is increasing rapidly worldwide and is accompanied by many complications, including impaired muscle regeneration. Obesity is known to inhibit AMP-activated protein kinase (AMPK) activity, which impedes mitochondrial biogenesis, myogenic differentiation and muscle regeneration. Resveratrol has an effective anti-obesity effect, but its effect on regeneration of muscle in obese mice remains to be tested. We hypothesized that resveratrol activates AMPK and mitochondrial biogenesis to improve muscle regeneration. Male C57BL/6J mice were fed a control diet or a 60% high-fat diet with or without resveratrol supplementation for 8 weeks and, then, the tibialis anterior muscle was subjected to cardiotoxin-induced muscle injury. Muscle tissue was collected at 3 and 7 d after injury. We found that resveratrol enhanced both proliferation and differentiation of satellite cells following injury in obese mice. Markers of mitochondrial biogenesis were upregulated in resveratrol-treated mice. In C2C12 myogenic cells, resveratrol activated AMPK and stimulated the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, which were associated with enhanced myogenic differentiation. Such effects of resveratrol were abolished by AMPKα1 ablation, showing the mediatory roles of AMPK. In summary, dietary resveratrol activates AMPK/ proliferator-activated receptor gamma coactivator 1-alpha axis to facilitate mitochondrial biogenesis and muscle regeneration impaired due to obesity.
肥胖症在全球范围内迅速增加，并伴有许多并发症，包括肌肉再生受损。肥胖症已知会抑制 AMP 激活的蛋白激酶（AMPK）的活性，从而阻碍线粒体生物发生、肌生成分化和肌肉再生。白藜芦醇具有有效的抗肥胖作用，但它对肥胖小鼠肌肉再生的影响仍有待检验。我们假设白藜芦醇通过激活 AMPK 和线粒体生物发生来改善肌肉再生。雄性 C57BL/6J 小鼠喂食对照饮食或 60%高脂肪饮食，或同时补充白藜芦醇 8 周，然后用心脏毒素诱导前胫骨肌损伤。在损伤后 3 天和 7 天收集肌肉组织。我们发现，白藜芦醇增强了肥胖小鼠损伤后卫星细胞的增殖和分化。在白藜芦醇处理的小鼠中，线粒体生物发生的标志物上调。在 C2C12 成肌细胞中，白藜芦醇激活了 AMPK，并刺激过氧化物酶体增殖物激活受体γ共激活因子 1-α的表达，这与增强的成肌分化有关。AMPKα1 缺失消除了白藜芦醇的这种作用，表明 AMPK 的介导作用。总之，饮食中的白藜芦醇激活了 AMPK/过氧化物酶体增殖物激活受体γ共激活因子 1-α轴，促进了肥胖引起的线粒体生物发生和肌肉再生受损。
