The constitutive lipid droplet protein PLIN2 regulates autophagy in liver

AbstractExcess triglyceride (TG) accumulation in the liver underlies fatty liver disease, a highly prevalent ailment. TG occurs in the liver sequestered in lipid droplets, the major lipid storage organelle. Lipid droplets are home to the lipid droplet proteins, the most abundant of which are the perilipins (PLINs), encoded by 5 different genes, Plin1 to Plin5. Of the corresponding gene products, PLIN2 is the only constitutive and ubiquitously expressed lipid droplet protein that has been used as a protein marker for lipid droplets. We and others reported that plin2−/− mice have an ∼60% reduction in TG content, and are protected against fatty liver disease. Here we show that PLIN2 overexpression protects lipid droplets against macroautophagy/autophagy, whereas PLIN2 deficiency enhances autophagy and depletes hepatic TG. The enhanced autophagy in plin2−/− mice protects against severe ER stress-induced hepatosteatosis and hepatocyte apoptosis. In contrast, hepatic TG depletion resulting from other genetic an...