This study investigates the interrelationship between autophagy and lipid metabolism, identifying a previously unknown function for autophagy in regulating intracellular lipid stores (macrolipophagy). During nutrient deprivation, cellular lipids stored as triglycerides in lipid droplets are hydrolyzed into fatty acids for energy. Autophagy, which delivers intracellular proteins and organelles to lysosomes for degradation and energy use, shares similarities in regulation and function with lipolysis but was not previously known to be interrelated. The study shows that inhibition of autophagy in cultured hepatocytes and mouse liver increases triglyceride storage in lipid droplets. This is further supported by the observation that loss of autophagy leads to decreased triglyceride breakdown and increased lipid accumulation. Additionally, lipid droplets and autophagic components co-localize during nutrient deprivation, and autophagic vacuoles containing lipid droplets are more abundant in starved conditions. In vivo studies in Atg7fl/fl-Alb-Cre mice, which have a hepatocyte-specific knockout of the autophagy gene Atg7, confirm that autophagy is crucial for maintaining hepatic lipid homeostasis. These findings suggest that autophagy plays a critical role in lipid metabolism and could have implications for human diseases characterized by lipid over-accumulation, such as metabolic syndrome.This study investigates the interrelationship between autophagy and lipid metabolism, identifying a previously unknown function for autophagy in regulating intracellular lipid stores (macrolipophagy). During nutrient deprivation, cellular lipids stored as triglycerides in lipid droplets are hydrolyzed into fatty acids for energy. Autophagy, which delivers intracellular proteins and organelles to lysosomes for degradation and energy use, shares similarities in regulation and function with lipolysis but was not previously known to be interrelated. The study shows that inhibition of autophagy in cultured hepatocytes and mouse liver increases triglyceride storage in lipid droplets. This is further supported by the observation that loss of autophagy leads to decreased triglyceride breakdown and increased lipid accumulation. Additionally, lipid droplets and autophagic components co-localize during nutrient deprivation, and autophagic vacuoles containing lipid droplets are more abundant in starved conditions. In vivo studies in Atg7fl/fl-Alb-Cre mice, which have a hepatocyte-specific knockout of the autophagy gene Atg7, confirm that autophagy is crucial for maintaining hepatic lipid homeostasis. These findings suggest that autophagy plays a critical role in lipid metabolism and could have implications for human diseases characterized by lipid over-accumulation, such as metabolic syndrome.