Liver-Specific Loss of Perilipin 2 Alleviates Hepatic Steatosis and Inflammation

Nonalcoholic fatty liver disease (NAFLD) covers a spectrum of conditions ranging from reversible steatosis, characterized by excess triglycerides (TG) stored in hepatic lipid droplets (LD) to the more serious inflammation-related nonalcoholic steatohepatitis (NASH). Overexpression of the primary hepatic LD protein, Perilipin 2 (Plin2) is associated with promoting two key features of NASH, i.e., hepatic lipid accumulation and increased inflammation, yet the role of Plin2 in the progression of NASH remains unclear. In the current study, Plin2 liver-specific knockout (Plin2L-/-) mice age-matched to floxed (Plin2fl/fl) control mice were challenged with a methionine choline deficient (MCD) diet to produce the NASH phenotype of increased hepatic TG levels through impairment of phosphatidylcholine (PC) synthesis and VLDL secretion. As expected, Plin2fl/fl mice fed the MCD exhibited elevated levels of TG concomitant with decreased PC and VLDL levels. In addition, liver weight, body weight, and histology indicated...