Autophagy regulates lipid metabolism

The intracellular storage and utilization of lipids are critical to maintain cellular energy homeostasis. During nutrient deprivation, cellular lipids stored as triglycerides in lipid droplets are hydrolysed into fatty acids for energy. A second cellular response to starvation is the induction of autophagy, which delivers intracellular proteins and organelles sequestered in double-membrane vesicles (autophagosomes) to lysosomes for degradation and use as an energy source. Lipolysis and autophagy share similarities in regulation and function but are not known to be interrelated. Here we show a previously unknown function for autophagy in regulating intracellular lipid stores (macrolipophagy). Lipid droplets and autophagic components associated during nutrient deprivation, and inhibition of autophagy in cultured hepatocytes and mouse liver increased triglyceride storage in lipid droplets. This study identifies a critical function for autophagy in lipid metabolism that could have important implications for human diseases with lipid over-accumulation such as those that comprise the metabolic syndrome. Lipid droplets are cytoplasmic organelles that store lipids such as triglycerides and cholesterol. Under conditions of nutrient deprivation, droplet triglycerides are hydrolysed to generate free fatty acids that are oxidized to provide energy. A second cellular response to starvation is autophagy, in which the cell digests its own components to provide nutrients. Singh et al. describe a novel function for autophagy in regulating lipid metabolism, which they term 'macrolipophagy'. In this process, lipid droplets and autophagic components associate during starvation and inhibition of autophagy increases lipid storage in lipid droplets. Autophagy promotes lipid hydrolysis and generation of free fatty acids by releasing the content of lipid droplets to lysosomes for degradation. This work identifies a critical role of autophagy in regulating lipid metabolism and may provide a new approach to the prevention of lipid accumulation in disease. Description of a novel function for autophagy in regulating lipid metabolism, called 'macrolipophagy', in which lipid droplets and autophagic components associate during starvation and inhibition of autophagy increases lipid storage in lipid droplets. A critical role of autophagy in regulating lipid metabolism is identified, and may provide a new approach to prevent lipid accumulation in disease.