Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Ethanol Extracts of Mori Folium Inhibit Adipogenesis Through Activation of AMPK Signaling Pathway in 3T3-L1 Preadipocytes

3T3-L1 세포에서 상엽이 유발하는 AMPK signaling pathway를 통한 adipogenesis 억제에 관한 연구

  • Ji, Seon Young (Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University) ;
  • Jeon, Keong Yoon (Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University) ;
  • Jeong, Jin Woo (Department of Biochemistry, Dongeui University College of Korean Medicine) ;
  • Hong, Su Hyun (Department of Biochemistry, Dongeui University College of Korean Medicine) ;
  • Huh, Man Kyu (Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University) ;
  • Choi, Yung Hyun (Department of Biochemistry, Dongeui University College of Korean Medicine) ;
  • Park, Cheol (Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University)
  • 지선영 (동의대학교 자연생활과학대학 분자생물학과) ;
  • 전경윤 (동의대학교 자연생활과학대학 분자생물학과) ;
  • 정진우 (동의대학교 한의과대학 생화학교실) ;
  • 홍수현 (동의대학교 한의과대학 생화학교실) ;
  • 허만규 (동의대학교 자연생활과학대학 분자생물학과) ;
  • 최영현 (동의대학교 한의과대학 생화학교실) ;
  • 박철 (동의대학교 자연생활과학대학 분자생물학과)
  • Received : 2016.11.28
  • Accepted : 2017.02.01
  • Published : 2017.02.28
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Abstract

Mori Folium, the leaf of Morus alba, is a traditional medicinal herb that shows various pharmacological activities such as antiinflammatory, antidiabetic, antimelanogenesis, antioxidant, antibacterial, antiallergic, and immunomodulatory activities. However, the mechanisms of their inhibitory effects on adipocyte differentiation and adipogenesis remain poorly understood. In the present study, we investigated the inhibition of adipocyte differentiation and adipogenesis by ethanol extracts of Mori Folium (EEMF) in 3T3-L1 preadipocytes. Treatment with EEMF suppressed the terminal differentiation of 3T3-L1 preadipocytes in a dose-dependent manner, as confirmed by a decrease in the lipid droplet number and lipid content through Oil Red O staining. EEMF significantly reduced the accumulation of cellular triglyceride, which is associated with a significant inhibition of pro-adipogenic transcription factors, including sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-${\gamma}$ ($PPAR{\gamma}$), and CCAAT/enhancer-binding proteins ${\alpha}$ ($C/EBP{\alpha}$) and ${\beta}$ ($C/EBP{\beta}$). In addition, EEMF potentially downregulated the expression of adipocyte-specific genes, including adipocyte fatty acid binding protein (aP2) and leptin. Furthermore, EEMF treatment effectively increased the phosphorylation of the AMP-activated protein kinase (AMPK) and acetyl CoA carboxylase (ACC); however, treatment with a potent inhibitor of AMPK, compound C, significantly restored the EEMF-induced inhibition of pro-adipogenic transcription factors and adipocyte-specific genes. These results together indicate that EEMF has preeminent effects on the inhibition of adipogenesis through the AMPK signaling pathway, and further studies will be needed to identify the active compounds in Mori Folium.

상엽은 뽕나무 잎을 건조한 약재로서 항염증, 항당뇨, 미백, 항산화, 항박테리아, 항알러지 및 면역조절 등과 같은 여러 가지 약리작용을 하는 것으로 알려져 있으나 항비만 효능에 대한 연구는 부족한 실정이다. 본 연구에서는 상엽 에탄올 추출물(ethanol extracts of Mori Folium, EEMF)이 유발하는 항비만 효능을 확인하기 위하여 3T3-L1 지방전구세포가 지방세포로 분화되는 과정에서 EEMF가 어떠한 영향을 미치는 지를 조사하였다. 3T3-L1 지방전구세포의 분화유도 시 EEMF를 처리하였을 경우 지방세포의 특징인 지방방울의 수 및 지방함량이 농도의 존적으로 감소하였으며, triglyceride의 생성도 억제되는 것으로 나타났다. 또한 EEMF는 pro-adipogenic transcription factors인 SREBP-1c, $PPAR{\gamma}$, $C/EBP{\alpha}$ 및 $C/EBP{\beta}$ 의 발현억제와 함께 adipocyte-specific genes인 aP2 및 Leptin의 발현억제도 유발하는 것으로 조사되었다. 특히 EEMF는 AMPK 및 ACC의 인산화를 억제하는 것으로 나타났지만 AMPK 억제제인 compound C를 이용하여 AMPK의 활성을 억제하였을 경우 EEMF에 의하여 유발되는 pro-adipogenic transcription factors 및 adipocyte-specific genes의 억제현상이 회복되었다. 이상의 결과에서 EEMF가 유발하는 adipogenesis의 억제는 AMPK signaling pathway의 활성화를 통하여 유발된다는 것을 알 수 있었으며, 추가적인 연구를 통하여 상엽에 함유되어 있는 유효성분에 대한 분석이 필요할 것으로 생각된다.

Keywords

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