Chronic obstructive pulmonary disease (COPD) is a systemic condition with significant extrapulmonary comorbidities. White adipose tissue (WAT) dysfunction, driven by cigarette smoke exposure, may contribute to systemic inflammation and disease progression. This study investigates whether oxidative stress mediates lung–adipose tissue crosstalk in COPD and whether targeting this pathway can mitigate both pulmonary and metabolic dysfunction. Male BALB/c mice were exposed to cigarette smoke for 8 or 24 weeks, with or without apocynin, an NADPH oxidase inhibitor. Lung and WAT tissues were analysed for inflammation, oxidative stress, adipokine expression, and mitochondrial function. Phosphoproteomic profiling was performed on lung tissue. In vitro, conditioned media from cigarette smoke-exposed bronchial epithelial cells and oxidatively primed adipocytes were used to assess reciprocal effects on adipocytes and epithelial cells. Cigarette smoke exposure induced airway inflammation, glucose intolerance, dyslipidemia, and WAT dysfunction, including increased lipolysis, oxidative stress, and adipokine imbalance. Apocynin treatment reduced oxidative stress, normalized adipokine profiles, and restored mitochondrial markers in WAT. Phosphoproteomic analysis revealed activation of MAPK, TNF, and Apelin signalling pathways in the lungs. Conditioned media experiments confirmed bidirectional crosstalk: epithelial-derived factors impaired adipocyte function, while dysfunctional adipocytes triggered oxidative stress and apoptosis in bronchial epithelial cells. Cigarette smoke-induced oxidative stress drives a pathological feedback loop between the lungs and WAT, contributing to COPD progression and systemic metabolic dysfunction. Targeting redox-sensitive pathways may offer therapeutic strategies to disrupt this lung–adipose axis and improve outcomes in COPD.
Wang et al. (Mon,) studied this question.