LAUSR

ABSTRACT Pro‐inflammatory cytokines, such as tumor necrosis factor alpha (TNF&agr;), may contribute to hepatic steatosis in the situation of excess lipid accumulation in farmed fish. Pigment epithelium‐derived factor (PEDF) is an endogenous anti‐inflammatory factor and promotes lipolysis. Accordingly, we isolated PEDF from grass carp and investigated its role in TNF&agr;‐induced hepatic steatosis. Sequence analysis showed that PEDF gene, which possesses 8 exons and 7 introns, encodes a protein with 409 amino acids. PEDF was a critical determinant of the transcriptional response to nutrient availability in grass carp. Endogenous PEDF was an intracellular protein with cytoplasmic distribution and directly interacts with adipose triglyceride lipase (ATGL), which might mediate PEDF‐induced lipolysis. TNF&agr; significantly promoted lipid accumulation in vivo and in vitro, accompanied with a decrease in mRNA levels of PEDF and peroxisome proliferator‐activated receptor alpha (PPAR&agr;). Recombinant PEDF and PPAR&agr; agonist diminished the TNF&agr;‐induced hepatic steatosis. Meanwhile, PPAR&agr; agonist caused an increase in PEDF expression, suggesting that TNF&agr; antagonizes the actions of PEDF possibly in a PPAR&agr;‐dependent manner. These findings suggest that PEDF is an important protective factor against hepatic steatosis induced by TNF&agr;, which provided a new therapeutic target for inflammation‐associated hepatic steatosis. HighlightsIdentified a full‐length DNA sequence of PEDF from grass carp.PEDF directly interacts with ATGL and down‐regulation of lipid accumulation in grass carp.TNF&agr; antagonizes the actions of PEDF though PPAR&agr;, and promotes hepatocyte steatosis.