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Berberine prevents free fatty acid‐induced lipid accumulation by activating ERK through sphingosine‐1‐phosphate receptor 2 in hepatocytes
Author(s) -
Zhou Xiqiao,
Shi Ruihua,
Studer Elaine,
Hylemon Phillip B,
Pandak William M,
Sanyal Arun J,
Zhou Huiping
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.751.19
Subject(s) - sphingosine 1 phosphate , berberine , chemistry , mapk/erk pathway , sphingosine , lipid signaling , sphingosine 1 phosphate receptor , s1pr1 , fatty acid , biochemistry , microbiology and biotechnology , receptor , phosphorylation , biology , cancer research , vascular endothelial growth factor a , vascular endothelial growth factor , vegf receptors
Free fatty acid (FFA)‐induced lipotoxicity plays a pivotal role in the pathogenesis of nonalcoholic fatty liver disease. Berberine (BBR), an isoquinoline alkaloid isolated from many medicinal herbs, has been used to treat various diseases including liver diseases for hundreds of years. However, the molecular mechanisms underlying the beneficial effects of BBR remain to be identified. This study was to determine the effect of BBR on FFA‐induced lipid accumulation in hepatocytes and further identify the potential mechanisms. Methods HepG2 cells, 293 cells stably transfected with GFP‐tagged sphingosine‐1‐phosphate receptor 2 (S1P 2 ), primary hepatocytes from wild type and S1P 2 −/− mice were used in this study. Cells were treated with palmitic acid (PA) with or without BBR. The intracellular lipid was stained with Oil Red O. Activation of ERK was determined by Western Blot analysis. The internalization of S1P 2 was detected by fluorescence microscopy. Results BBR dose‐dependently inhibited PA‐induced lipid accumulation by activating ERK in hepatocytes. In the absence of S1P 2 , BBR failed to inhibit PA‐induced lipid accumulation. In addition, BBR‐induced ERK activation was inhibited by pertussis toxin. Moreover, BBR induced S1P 2 internalization. Conclusion BBR prevents FFA‐induced lipotoxicity by activating the ERK signaling pathway through S1P 2 in hepatocytes.