Autophagy in lipid metabolism

Autophagy is a complex and highly regulated cellular process essential for maintaining homeostasis in adipose tissue by modulating adipocyte differentiation, lipogenesis, and lipolysis. Although lipids are primarily known as energy-storage compounds, they also play a role in triglyceride transport, intracellular communication via steroid hormones, organ protection, and thermoregulation. Lipid metabolism relies on the dynamic balance between synthesis, storage and degradation of key lipid classes such as: triglycerides, sterols and phospholipids. Among the pathways controlling lipid metabolism, autophagy plays a critical role by facilitating lipid degradation via enzymatic lipolysis and lipophagy. The latter emerges as a central mechanism in selectively degrading lipid droplets (LD), thus preventing lipid overload and lipotoxicity. Dysregulation of autophagy contributes to the onset and progression of various metabolic disorders, including obesity, non-alcoholic fatty liver disease, and lysosomal storage diseases. This review provides a comprehensive overview of the molecular mechanisms underpinning autophagy, its role in lipid metabolism, and its pathological relevance in lipid-associated disorders, offering insights into potential therapeutic strategies targeting autophagic pathways for restoring lipid balance.