KMID : 0043320150380122153
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Archives of Pharmacal Research 2015 Volume.38 No. 12 p.2153 ~ p.2162
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Anti-adipogenic effect of epiberberine is mediated by regulation of the Raf/MEK1/2/ERK1/2 and AMPK¥á/Akt pathways
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Choi Jae-Sue
Kim Ji-Hye Ali Yousof Jung Hee-Jin Min Byung-Sun Choi Ran-Joo Kim Gun-Do Jung Hyun-Ah
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Abstract
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It has been reported that alkaloids derived from Coptis chinensis exert anti-adipogenic activity on 3T3-L1 adipocytes by downregulating peroxisome proliferation-activity receptor-¥ã (PPAR-¥ã) and CCAAT/enhancer binding protein-¥á (C/EBP-¥á). However, the signaling-based mechanism of the inhibitory role of epiberberine in the early stages of 3T3-L1 adipocyte differentiation is uncharacterized. Here, we show that epiberberine had inhibitory effects on adipocyte differentiation and significantly decreased lipid accumulation by downregulating an adipocyte-specific transcription factor, sterol regulatory element-binding protein-1 (SREBP-1). Furthermore, we observed that epiberberine markedly suppressed the differentiation-mediated phosphorylation of components of both the Raf/mitogen-activated protein kinase 1 (MEK1)/extracellular signal-regulated protein kinase 1/2 (ERK1/2) and AMP-activated protein kinase-¥á1 (AMPK¥á)/Akt pathways. In addition, gene expression of fatty acid synthase (FAS) was significantly inhibited by treatment with epiberberine during adipogenesis. These results indicate that the anti-adipogenic mechanism of epiberberine is associated with inhibition of phosphorylation of Raf/MEK1/ERK1/2 and AMPK¥á/Akt, followed by downregulation of the major transcription factors of adipogenesis, such as PPAR-¥ã, C/EBP-¥á, and SREBP-1, and FAS. Taken together, this study suggests that the anti-adipogenic effect of epiberberine is mediated by downregulation of the Raf/MEK1/ERK1/2 and AMPK¥á/Akt pathways during 3T3-L1 adipocyte differentiation. Moreover, the anti-adipogenic effects of epiberberine were not accompanied by modulation of ¥â-catenin.
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KEYWORD
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Obesity, Adipogenesis, AMPK¥á/Akt, Raf/MEK1/ERK1/2, Epiberberine
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