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The role of leptin in lipid metabolism in fatty degenerated hepatocytes of the grass carp Ctenopharyngodon idellus

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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.

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Abbreviations

PPARα:

Peroxisome proliferators-activated receptor-alpha

PPARβ:

Peroxisome proliferators-activated receptor-beta

PPARγ:

Peroxisome proliferators-activated receptor-gamma

HSL:

Hormone-sensitive lipase

ATGL:

Adipose triglyceride lipase

PGC-1α:

Peroxisome proliferators-activated receptor gamma coactivator-1 alpha

CPT-I:

Carnitine palmitoyl transferase-I

UCP1:

Uncoupling protein 1

UCP2:

Uncoupling protein 2

FFA:

Free fatty acids

SCD1:

Stearoyl-CoA desaturase 1

LPL:

Lipoprotein lipase

Lep:

Leptin

LepR:

Leptin receptor

JAK-STAT:

Just another kinase/signal transducer and activator of transcription

IRS-PI(3)K:

Insulin receptor substrate (IRS)-phosphatidylinositol-3-OH-kinase

NAFL:

Nonalcoholic fatty liver

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Acknowledgments

We are very grateful to Dr. Jeffrey T. Silverstein, Dr. Hong Ji, and Dr. Guoliang Meng for their helpful review of the manuscript. This work was financially supported by the National Natural Science Foundation of China (31172420 and 31072219), the National Basic Research Program of China (2009CB118702), the Special Fund for Agro-Scientific Research in the Public Interest of China (201003020) and the Fundamental Research Funds for the Central Universities (2010PY010 and 2011PY030) and the China Postdoctoral Science Foundation (Project No. 52201-12971).

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  1. College of Fisheries, Hua Zhong Agricultural University, Wuhan, 430070, China

    Rong-Hua Lu, Xu-Fang Liang, Min Wang, Yi Zhou, Xiao-Li Bai & Yan He

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  1. Rong-Hua Lu
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  2. Xu-Fang Liang
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Lu, RH., Liang, XF., Wang, M. et al. The role of leptin in lipid metabolism in fatty degenerated hepatocytes of the grass carp Ctenopharyngodon idellus . Fish Physiol Biochem 38, 1759–1774 (2012). https://doi.org/10.1007/s10695-012-9673-6

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