Metabolism and lifespan of Drosophila melanogaster after smoke exposure regulation following Wnt pathway activation

Chronic obstructive pulmonary disease (COPD) is the leading cause of mortality and morbidity worldwide and is characterised by incomplete reversibility of expiratory airflow limitation, dysregulated chronic inflammation and emphysematous destruction.The WNT signaling cascade controls a myriad of biological phenomena throughout the development and adult life of all animals.The regulation of WNT signaling in the development of COPD/emphysema by cigarette smoke exposure leads to dysregulation of classical and non-classical dysregulation of the WNT signalling pathway, which leads to oxidative stress, apoptosis/proliferation, inflammation, mucus hypersecretion, protease/anti-protease imbalance, autophagy, senescence, metabolic reprogramming, mitochondrial dysfunction or altered stem/progenitor cell renewal. All these cellular processes are involved in the pathogenesis of chronic bronchitis or emphysema through increased lung injury and impaired lung repair. We used a simple cigarette smoke-induced Drosophila model of COPD based on chronic cigarette smoke exposure that encapsulates the main pathological features of the disease and can therefore be used to investigate new therapeutic strategies. We used this model to examine the role of WNT signalling in COPD and showed that overexpression of WNT/β-catenin reversed the premature death, reduced physical activity, reduced body fat and protein, increased metabolic rate and reduced tolerance to hypoxia caused by Chronic cigarette smoke exposured. While many studies have focused on the typical WNT/β-catenin protein signalling pathway, recent reports have highlighted that the atypical WNT signalling pathway may also have a significant impact on chronic lung disease. These findings provide potential therapeutic targets for intervention in COPD/emphysema. Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany