Objective To investigate the role of the adenosine monophosphate-activated protein kinase (AMPK)-ULK1-mediated autophagy pathway in cigarette smoke (CS)-induced skeletal muscle atrophy. Methods C57BL/6 mice were used as subjects and divided into control group and cigarette smoke exposure group (CS group). The model of pulmonary emphysema was established by exposing C57BL/6 mice to CS for 24 weeks. Hematoxylin-eosin (HE) staining was used to observe the morphological changes in the alveoli and gastrocnemius muscle. The number of autophagosomes in the muscle tissue was quantified by transmission electron microscopy. The expression of autophagy-related proteins was detected using immunofluorescence and western blotting. A skeletal muscle atrophy model was established by treating C2C12 myoblasts with cigarette smoke extract (CSE) and divided into a control group and a CSE group. Additionally, C2C12 cell lines with AMPK overexpression were constructed using lentivirus. Further interventions were performed using the autophagy inhibitor 3-Methyladenine (3-MA), the AMPK activator AICAR, and the AMPK inhibitor Dorsomorphin (Compound C). Western blot was applied to detect the expression levels of autophagy-related proteins (LC3B, p62, Beclin1) and key proteins of the AMPK/ULK1 pathway (phosphorylated AMPK and phosphorylated ULK1). Autophagosomes in cells were detected using mCherry-GFP-LC3B-labeled adenovirus. Changes in the diameter of C2C12 myotubes were examined by immunofluorescence. Results CS exposure induced skeletal muscle atrophy in mice, accompanied by enhanced autophagy mediated by the AMPK-ULK1 pathway. In vitro, compared with the control group, the CSE group exhibited AMPK pathway activation and significantly increased expression of autophagy-related proteins LC3B, p62, and Beclin1, along with decreased myotube diameter. The AMPK activator AICAR and AMPK overexpression also promoted skeletal muscle autophagy and induced myotube atrophy, while the AMPK inhibitor Compound C effectively alleviated CSE-induced skeletal muscle autophagy and myotube atrophy. Conclusion CS can induce skeletal muscle atrophy by activating the AMPK-ULK1 signaling pathway and enhancing the subsequent autophagic process.
Citation：
YE Yuanyuan, XIE Yuqing, TAN Yufen, LI Jie, LIANG Tong, HUANG Lihua, XIONG Guolin, HUANG Cuibi, BIN Yanfei. Cigarette smoke exposure promotes skeletal muscle atrophy in mice through enhancing AMPK-ULK1 activity mediated autophagy. Chinese Journal of Respiratory and Critical Care Medicine, 2026, 25(4): 275-283. doi: 10.7507/1671-6205.202512042
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Copyright ? the editorial department of Chinese Journal of Respiratory and Critical Care Medicine of West China Medical Publisher. All rights reserved
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