肥胖诱导的骨骼肌萎缩机制研究进展

Advances on the Mechanism of Obesity-induced Skeletal Muscle Atrophy

骨骼肌是人体氨基酸和蛋白质的主要贮存、代谢库,其正常功能和代谢过程受到多种病理因素的影响。骨骼肌萎缩发生于骨骼肌稳态严重失衡状态下,对患者生活和社会医疗造成了沉重负担。近年来,由于世界肥胖人群数量激增,肥胖诱导的骨骼肌萎缩正日益成为公共卫生的严峻挑战之一。肥胖诱导的骨骼肌萎缩过程涉及多种信号分子或通路的改变,如泛素蛋白酶系统、自噬溶酶体系统、胰岛素/IGF1-PI3K-Akt、肌肉生长抑制素、白细胞介素-6、肿瘤坏死因子等;这些信号分子或通路在肥胖状态下被激活或抑制后,可共同影响蛋白质合成/分解平衡进而造成骨骼肌萎缩。基于上述信号分子或通路,系统总结并讨论了肥胖诱导的骨骼肌萎缩机制,以期为寻找缓解/治疗肥胖诱导的肌萎缩靶点和进一步开发利用天然植物化学物提供理论依据。

Skeletal muscle is the main storage and metabolic reservoir of amino acids and proteins in the body,and its normal function and metabolic processes are affected by a variety of pathological factors.Skeletal muscle atrophy occurs in a state of severe imbalance in skeletal muscle homeostasis,which imposes a heavy burden on patients’lives and social and medical care.In recent years,obesity-induced skeletal muscle atrophy is increasingly becoming a serious public health challenge due to the proliferation of obesity in the world.Obesity-induced skeletal muscle atrophy involves changes in various signaling molecules or pathways,such as ubiquitin protease system,autophagy-lysosomal system,insulin/IGF1-PI3K-Akt,myostatin,interleukin-6,tumor necrosis factor,etc.After these signal molecules or pathways are activated or inhibited in the state of obesity,they can jointly affect the balance of protein synthesis/catabolism and further cause skeletal muscle atrophy.Based on the above-mentioned signaling molecules or pathways,this study systematically summarized and discussed the mechanism underlying obesity-induced skeletal muscle atrophy,hoping to provide theoretical references for exploring preventive or therapeutic targets of obesity-induced muscle atrophy,and to extend the development and utilization of natural phytochemicals.