Lipophagy in chronic obstructive pulmonary disease: Mechanistic insights and emerging therapeutic targets

Chronic obstructive pulmonary disease (COPD), characterized by persistent airflow limitation and chronic inflammation, still lacks therapies that truly modify the disease course. Emerging studies suggest that lipophagy may occupy a pivotal position in pulmonary and systemic lipid homeostasis in COPD. This review aims to integrate evidence regarding how lipophagy reshapes cellular metabolism and interfaces with canonical pathogenic processes in COPD, and to evaluate its translational prospects. We delineate, in the context of COPD, the links between lipophagy and glycolysis, fatty-acid β-oxidation, lipid synthesis and catabolism, and mitochondrial function. In this narrative review, we integrate and critically discuss evidence on how lipophagy reshapes cellular metabolism and interfaces with canonical pathogenic processes in COPD. We summarize mechanistic links between lipophagy imbalance and lipid-droplet accumulation, inflammation and immune responses, oxidative stress and proteostasis disruption, apoptosis, and cellular senescence, and we discuss extra-pulmonary manifestations including skeletal-muscle fat infiltration and satellite-cell dysfunction. We posit that lipophagy resides at the intersection of metabolism, organelle quality control, and inflammatory signaling in COPD; "calibrated reconstruction" of lipophagy may re-establish bioenergetics and mitigate lipotoxicity, thereby offering a new perspective for developing lipophagy-based interventions to improve COPD progression.