Emerging Role of Natural Lipophagy Modulators in MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is a seriously increasing liver disorder affecting nearly 32% of adults globally. Hepatic triglycerides (TG) accumulation is the hallmark of MASLD which results from dysregulated lipid and fatty acid uptake, increased de novo lipogenesis (DNL), and decreased lipid removal. More recently, selective autophagy of lipid droplets (LDs), termed lipophagy, has emerged to be closely associated with disrupted hepatic lipid homeostasis. Recent studies indicated that a series of natural products have shown their advantages as an alternative approach in attenuating MASLD via regulating lipophagy in vivo and in vitro. Therefore, lipophagy could be a new approach for natural products to improve MASLD. This review aims to provide a comprehensive overview about the interrelationship between dysregulated lipid metabolism, lipophagy, and MASLD pathogenesis. In addition, the role of some natural products as lipophagy modulators and their impact on MASLD will be discussed.