Altered hepatic lipid droplet morphology and lipid metabolism in fasted Plin2-null mice

Perilipin 2 (Plin2) binds to the surface of hepatic lipid droplets (LDs) with expression levels that correlate with triacylglyceride (TAG) content. We investigated if Plin2 is important for hepatic LD storage in fasted or high-fat diet-induced obese Plin2^+/+ and Plin2^-/- mice. Plin2^-/- mice had comparable body weights, metabolic phenotype, glucose tolerance, and circulating TAG and total cholesterol levels compared with Plin2^+/+ mice, regardless of the dietary regime. Both fasted and high-fat fed Plin2^-/- mice stored reduced levels of hepatic TAG compared with Plin2^+/+ mice. Fasted Plin2^-/- mice stored fewer but larger hepatic LDs compared with Plin2^+/+ mice. Detailed hepatic lipid analysis showed substantial reductions in accumulated TAG species in fasted Plin2^-/- mice compared with Plin2^+/+ mice, whereas cholesteryl esters and phosphatidylcholines were increased. RNA-Seq revealed minor differences in hepatic gene expression between fed Plin2^+/+ and Plin2^-/- mice, in contrast to marked differences in gene expression between fasted Plin2^+/+ and Plin2^-/- mice. Our findings demonstrate that Plin2 is required to regulate hepatic LD size and storage of neutral lipid species in the fasted state, while its role in obesity-induced steatosis is less clear.