Jin Jun-Hui, Wen Deng-Tai, Chen Yi-Ling, Hou Wen-Qi
Department of Physical Education, Ludong University, 264025 Yantai, Shandong, China.
Department of Physical Education, Yichun University, 336000 Yichun, Jiangxi, China.
Front Biosci (Landmark Ed). 2023 Jan 18;28(1):16. doi: 10.31083/j.fbl2801016.
Obesity appears to significantly reduce physical activity, but it remains unclear whether this is related to obesity-induced damage to skeletal muscle (SM) and heart muscle (HM). Endurance exercise (EE) reduces obesity-induced defects in SM and HM, but its molecular mechanism is poorly understood.
The UAS/GAL4 system was used to construct the regulation of SM-specific FOXO gene expression in , and the transgenic was subjected to EE and high-fat diet (HFD) intervention.
The structure and function of SM and HM were impaired by a HFD and muscle-FOXO-specific RNAi (MFSR), including reduced climbing speed and climbing endurance, reduced fractional shortening of the heart, damaged myofibrils, and reduced mitochondria in HM. Besides, a HFD and MFSR increased triglyceride level and malondialdehyde level, decreased the Sirt1 and FOXO protein level, and reduced carnitine palmityl transferase I, superoxide dismutase, and catalase activity level, and they dow-regulated FOXO and bmm expression level in SM and HM. On the contrary, both muscle FOXO-specific overexpression (MFSO) and EE prevented abnormal changes of SM and HM in function, structure, or physiology caused by HFD and MFSR. Besides, EE also prevented defects of SM and HM induced by MFSR.
Current findings confirmed MFSO and EE protected SM and heart from defects caused by a HFD via enhancing FOXO-realated antioxidant pathways and lipid catabolism. FOXO played a vital role in regulating HFD-induced defects in SM and HM, but FOXO was not a key regulatory gene of EE against damages in SM and HM. The mechanism was related to activity of Sirt1/FOXO/SOD (superoxide dismutase), CAT (catalase) pathways and lipid catabolism in SM and HM.
肥胖似乎会显著降低身体活动能力，但肥胖是否会导致骨骼肌（SM）和心肌（HM）损伤尚不清楚。耐力运动（EE）可减少肥胖引起的SM和HM缺陷，但其分子机制仍不清楚。
利用UAS/GAL4系统构建果蝇中SM特异性FOXO基因表达的调控，对转基因果蝇进行EE和高脂饮食（HFD）干预。
HFD和肌肉特异性FOXO RNA干扰（MFSR）损害了SM和HM的结构和功能，包括攀爬速度和攀爬耐力降低、心脏缩短分数降低、肌原纤维受损以及HM中线粒体减少。此外，HFD和MFSR增加了甘油三酯水平和丙二醛水平，降低了Sirt1和FOXO蛋白水平，降低了肉碱棕榈酰转移酶I、超氧化物歧化酶和过氧化氢酶活性水平，并下调了SM和HM中FOXO和bmm的表达水平。相反，肌肉特异性FOXO过表达（MFSO）和EE均能预防HFD和MFSR引起的SM和HM在功能、结构或生理上的异常变化。此外，EE还能预防MFSR诱导的SM和HM缺陷。
目前的研究结果证实，MFSO和EE通过增强FOXO相关的抗氧化途径和脂质分解代谢，保护SM和心脏免受HFD引起的缺陷。FOXO在调节HFD诱导的SM和HM缺陷中起重要作用，但FOXO不是EE抵抗SM和HM损伤的关键调控基因。其机制与SM和HM中Sirt1/FOXO/超氧化物歧化酶（SOD）、过氧化氢酶（CAT）途径的活性以及脂质分解代谢有关。
