Two weeks smoking cessation reverses cigarette smoke-induced skeletal muscle atrophy and mitochondrial dysfunction in mice

Ajime, Tom Tanjeko, Serré, Jef, Wüst, Rob CI, Messa, Guy Anselme Mpaka, Poffé, Chiel, Swaminathan, Anandini, Maes, Karen, Janssens, Wim, Troosters, Thierry, Degens, Hans ORCID: https://orcid.org/0000-0001-7399-4841 and Gayan-Ramirez, Ghislaine (2021) Two weeks smoking cessation reverses cigarette smoke-induced skeletal muscle atrophy and mitochondrial dysfunction in mice. Nicotine & Tobacco Research, 23 (1). pp. 143-151. ISSN 1462-2203

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Abstract

Introduction Apart from its adverse effects on the respiratory system, cigarette smoking also induces skeletal muscle atrophy and dysfunction. Whether short-term smoking cessation can restore muscle mass and function is unknown. We therefore studied the impact of 1- and 2-weeks smoking cessation on skeletal muscles in a mouse model. Methods Male mice were divided into 4 groups: Air-exposed (14 weeks); cigarette smoke (CS)-exposed (14 weeks); CS-exposed (13 weeks) followed by 1-week cessation; CS-exposed (12 weeks) followed by 2 weeks cessation to examine exercise capacity, physical activity levels, body composition, muscle function, capillarization, mitochondrial function and protein expression in the soleus, plantaris and diaphragm muscles. Results CS-induced loss of body and muscle mass was significantly improved within 1 week of cessation due to increased lean and fat mass. Mitochondrial respiration and protein levels of the respiratory complexes in the soleus were lower in CS-exposed mice, but similar to control values after 2 weeks of cessation. Exposing isolated soleus muscles to CS extracts reduced mitochondrial respiration that was reversed after removing the extract. While physical activity was reduced in all groups, exercise capacity, limb muscle force, fatigue resistance, fiber size and capillarization and diaphragm cytoplasmic HIF-1α were unaltered by CS-exposure. However, CS-induced diaphragm atrophy and increased capillary density was not seen after 2 weeks of smoking cessation. Conclusion In male mice, two weeks smoking cessation reversed smoking-induced mitochondrial dysfunction, limb muscle mass loss and diaphragm muscle atrophy, highlighting immediate benefits of cessation on skeletal muscles.