title: Pigment epithelium-derived factor improves TNFα-induced hepatic steatosis in grass carp (Ctenopharyngodon idella).
abstract: Pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNFα), 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 TNFα-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. TNFα significantly promoted lipid accumulation in vivo and in vitro, accompanied with a decrease in mRNA levels of PEDF and peroxisome proliferator-activated receptor alpha (PPARα). Recombinant PEDF and PPARα agonist diminished the TNFα-induced hepatic steatosis. Meanwhile, PPARα agonist caused an increase in PEDF expression, suggesting that TNFα antagonizes the actions of PEDF possibly in a PPARα-dependent manner. These findings suggest that PEDF is an important protective factor against hepatic steatosis induced by TNFα, which provided a new therapeutic target for inflammation-associated hepatic steatosis.
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Yang
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China. Electronic address: jihong@nwsuaf.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
authors.forename: Xiao-Chen
authors.initials: XC
authors.lastname: Shi
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Aquaculture Nutrition and Environmental Health, School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Du
authors.affiliation: Laboratory of Aquaculture Nutrition and Environmental Health, School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Li-Qiao
authors.initials: LQ
authors.lastname: Chen
mesh_terms: D000818:Animals; D002347:Carps / Q000276:immunology*; D003001:Cloning, Molecular; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005234:Fatty Liver / Q000276:immunology*; D005393:Fish Diseases / Q000276:immunology*; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D040342:Genetic Structures; D007249:Inflammation / Q000276:immunology*; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D047493:PPAR alpha / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D029941:Fish Proteins; D008049:Lipase; D009414:Nerve Growth Factors; D047493:PPAR alpha; D015843:Serpins; D014409:Tumor Necrosis Factor-alpha; D000099174:Pigment Epithelium-Derived Factor
keywords: Grass carp (Ctenopharyngodon idella); Hepatic steatosis; PEDF; PPARα; TNFα