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Anti-adipogenic effect of epiberberine is mediated by regulation of the Raf/MEK1/2/ERK1/2 and AMPKα/Akt pathways

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Abstract

It has been reported that alkaloids derived from Coptis chinensis exert anti-adipogenic activity on 3T3-L1 adipocytes by downregulating peroxisome proliferation-activity receptor-γ (PPAR-γ) and CCAAT/enhancer binding protein-α (C/EBP-α). 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-α1 (AMPKα)/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 AMPKα/Akt, followed by downregulation of the major transcription factors of adipogenesis, such as PPAR-γ, C/EBP-α, 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 AMPKα/Akt pathways during 3T3-L1 adipocyte differentiation. Moreover, the anti-adipogenic effects of epiberberine were not accompanied by modulation of β-catenin.

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Acknowledgments

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2012R1A6A1028677).

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    Authors and Affiliations

    1. Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea

      Jae Sue Choi, Md. Yousof Ali & Hee Jin Jung

    2. Department of Microbiology, Pukyong National University, Busan, 608-737, Republic of Korea

      Ji-Hye Kim & Gun-Do Kim

    3. College of Pharmacy, Catholic University of Daegu, Gyeongbuk, 712-702, Republic of Korea

      Byung-Sun Min

    4. Department of Pharmacology, Angiogenesis & Chinese Medicine Laboratory, University of Cambridge, Cambridge, UK

      Ran Joo Choi

    5. Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, 561-756, Republic of Korea

      Hyun Ah Jung

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    Jae Sue Choi and Ji-Hye Kim have equally contributed to this work.

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    Choi, J.S., Kim, JH., Ali, M.Y. et al. Anti-adipogenic effect of epiberberine is mediated by regulation of the Raf/MEK1/2/ERK1/2 and AMPKα/Akt pathways. Arch. Pharm. Res. 38, 2153–2162 (2015). https://doi.org/10.1007/s12272-015-0626-3

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