Hepatic perilipin 5 promotes lipophagy and alters lipid droplet and mitochondrial dynamics

Lipid droplets (LDs) are energy‐storage organelles which are composed of a lipid core, mainly triacylglycerol, surrounded by a phospholipid monolayer. In addition, LDs are coated with hundreds of proteins including members of the perilipin family. Perilipin 5 (PLIN5) is highly expressed in oxidative tissues including the liver and in response to fasting. PLIN5 is thought to play a key role in uncoupling LD accumulation for lipotoxicity and mitochondrial dysfunction. It is generally accepted that PLIN5 influences LDs turnover through its binding and inhibition of lipolytic enzymes and also bridges LDs and mitochondria, which is thought to facilitate fatty acid transfer. The objective of these studies was to characterize the mechanism through which PLIN5 influences hepatic LD turnover in fed and fasting conditions. We employed anti‐sense oligonucleotides to ablate hepatic PLIN5 in vivo and used overexpression and knockdown approaches in primary hepatocytes. Both in vitro and in vivo studies revealed that PLIN5 ablation blocked autophagy and lipophagy, the lysosomal degradation LDs. Using autophagy inhibitors, we found that PLIN5 promoted autophagic flux, LD turnover and oxidation of LD‐derived fatty acids under fasting conditions. Moreover, we isolated cytosol and LD‐associated mitochondria and measured rates of fatty acid oxidation and protein expression. Cytosolic mitochondrial had increased fatty acid oxidation and expression proteins involved in fatty acid/oxidative metabolism, but ablation of PLIN5 normalized the differences between the two mitochondrial populations. In conclusion, PLIN5 promotes autophagy/lipophagy to influence LD turnover and plays a critical role in mitochondrial oxidative metabolism. Support or Funding Information National Institute of diabetes and digestive and kidney diseaseAmerican diabetes accociationNational Instituite on aging National Natural Science Foundation of China (NSFC 31671945)China Scholarship Council This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .