title: Anti-adipogenic effect of epiberberine is mediated by regulation of the Raf/MEK1/2/ERK1/2 and AMPKα/Akt pathways.
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.
authors.affiliation: Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea.
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Microbiology, Pukyong National University, Busan, 608-737, Republic of Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea.
authors.forename: Md Yousof
authors.initials: MY
authors.lastname: Ali
authors.affiliation: Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Jung
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongbuk, 712-702, Republic of Korea.
authors.forename: Byung-Sun
authors.initials: BS
authors.lastname: Min
authors.affiliation: Department of Pharmacology, Angiogenesis & Chinese Medicine Laboratory, University of Cambridge, Cambridge, UK.
authors.forename: Ran Joo
authors.initials: RJ
authors.lastname: Choi
authors.affiliation: Department of Microbiology, Pukyong National University, Busan, 608-737, Republic of Korea.
authors.forename: Gun-Do
authors.initials: GD
authors.lastname: Kim
authors.affiliation: Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, 561-756, Republic of Korea. jungha@jbnu.ac.kr.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Jung
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D048490:raf Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D019440:Anti-Obesity Agents; D004365:Drugs, Chinese Herbal; D001599:Berberine; C061432:epiberberine; C548179:Prkaa1 protein, mouse; D051058:Oncogene Protein v-akt; D048490:raf Kinases; D020928:Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482127:Map2k1 protein, mouse; C482129:Map2k2 protein, mouse
keywords: AMPKα/Akt; Adipogenesis; Epiberberine; Obesity; Raf/MEK1/ERK1/2