title: The role of leptin in lipid metabolism in fatty degenerated hepatocytes of the grass carp Ctenopharyngodon idellus.
abstract: Leptin (Lep) is a key factor in the regulation of energy homeostasis in mammals, but its role in the fatty degenerated hepatocytes of the grass carp Ctenopharyngodon idellus is still unknown. The aim of our study is to determine the underlying mechanism and possible effects of C. idellus Lep function in lipid metabolism in C. idellus fatty degenerated hepatocytes. Fatty degenerated hepatocytes of C. idellus were established through treatment with media containing 0.1 % lipid emulsion (LE). Hepatic triglycerides had markedly accumulated in the treated hepatocytes 48 h later. Furthermore, we demonstrated that Lep dose dependently promoted the release of glycerol, but not FFA, in fatty degenerated hepatocytes. We also found that Lep affected the expression of key genes related to lipid metabolism at the transcriptional and translational levels. A total of ten genes, including HSL, ATGL, PPARα, PPARβ, UCP1, UCP2, PGC-1α, and CPTIα-1b, were markedly upregulated, while SCD1a and PPARγ were downregulated with Lep treatment. Moreover, the protein levels of HSL and ATGL and the LPL activity also significantly increased. The Lep-induced lipolysis was disrupted by the JAK-STAT inhibitor AG490, suggesting that JAK-STAT signaling pathways were involved in the process of Lep-induced lipolysis. Using the IRS-PI(3)K-specific inhibitor W1628, we found that only the Lep-induced downregulation of PPARγ was reduced. This result indicated that the IRS-PI(3)K signaling pathway was involved in the regulation of the adipogenic gene PPARγ. Overall, our results provided evidence that Lep directly stimulated JAK-STAT signaling-mediated lipolysis and fatty acid β-oxidation gene expression in the fatty degenerated hepatocytes of C. idellus and inhibited the adipogenesis mediated by the IRS-PI(3)K signaling pathway.
authors: College of Fisheries, Hua Zhong Agricultural University, Wuhan, 430070, China.
authors: Rong-Hua
authors: RH
authors: Lu
authors: College of Fisheries, Hua Zhong Agricultural University, Wuhan, 430070, China. xfliang@mail.hzau.edu.cn.
authors: Xu-Fang
authors: XF
authors: Liang
authors: College of Fisheries, Hua Zhong Agricultural University, Wuhan, 430070, China.
authors: Min
authors: M
authors: Wang
authors: College of Fisheries, Hua Zhong Agricultural University, Wuhan, 430070, China.
authors: Yi
authors: Y
authors: Zhou
authors: College of Fisheries, Hua Zhong Agricultural University, Wuhan, 430070, China.
authors: Xiao-Li
authors: XL
authors: Bai
authors: College of Fisheries, Hua Zhong Agricultural University, Wuhan, 430070, China.
authors: Yan
authors: Y
authors: He
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002347:Carps / Q000378:metabolism*; D002460:Cell Line; D005230:Fatty Acids, Nonesterified; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology*; D008055:Lipids / Q000009:adverse effects*; D010084:Oxidation-Reduction; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism
chemical_list: D005230:Fatty Acids, Nonesterified; D020738:Leptin; D008055:Lipids; D047495:PPAR gamma; D054411:Receptors, Leptin; D002787:Sterol Esterase