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Effects of Polygonatum sibiricum rhizome extract on lipid and energy metabolism in high-fat diet-induced obese mice

고지방 식이 유도 비만 마우스 모델에서 황정 추출물의 지방질 및 에너지 대사 관련 유전자에 대한 효능 연구

  • Jeon, Woo-Jin (Research Laboratories, Ildong Pharmaceutical Co., Ltd.) ;
  • Kim, Ji-Young (Research Laboratories, Ildong Pharmaceutical Co., Ltd.) ;
  • Oh, Ik-Hoon (Research Laboratories, Ildong Pharmaceutical Co., Ltd.) ;
  • Lee, Do-Seop (Research Laboratories, Ildong Pharmaceutical Co., Ltd.) ;
  • Shon, Suh-Youn (Research Laboratories, Ildong Pharmaceutical Co., Ltd.) ;
  • Seo, Yun-Ji (Research Laboratories, Ildong Pharmaceutical Co., Ltd.) ;
  • Yeon, Seung-Woo (Research Laboratories, Ildong Pharmaceutical Co., Ltd.) ;
  • Kang, Jae-Hoon (Research Laboratories, Ildong Pharmaceutical Co., Ltd.)
  • 전우진 (일동제약(주) 중앙연구소) ;
  • 김지영 (일동제약(주) 중앙연구소) ;
  • 오익훈 (일동제약(주) 중앙연구소) ;
  • 이도섭 (일동제약(주) 중앙연구소) ;
  • 손서연 (일동제약(주) 중앙연구소) ;
  • 서윤지 (일동제약(주) 중앙연구소) ;
  • 연승우 (일동제약(주) 중앙연구소) ;
  • 강재훈 (일동제약(주) 중앙연구소)
  • Received : 2016.09.13
  • Accepted : 2016.12.21
  • Published : 2017.04.30

Abstract

In this study, factors involved in lipid and energy metabolism following treatment with ethanolic extract of the Polygonatum sibiricum rhizome (ID1216) were evaluated in high-fat diet-induced obese mice. ID1216-treated mice showed a significant reduction in weight gain compared to non-treated mice. ID1216 treatment increased the protein levels of AMP-dependent protein kinase, sirtuin1, peroxisome proliferator-activated receptor ${\gamma}$ coactivator 1-${\alpha}$ ($PGC1{\alpha}$), peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) and uncoupling proteins in the adipose tissue, liver and muscle compared to vehicle treatment. Analysis of downstream signals of the sirtuin1 $PGC1{\alpha}$-$PPAR{\alpha}$ pathway showed that ID1216 regulates the expression of ${\beta}$-oxidation related genes such as acyl-CoA oxidase, carnitine palmitoyltransferase1, acyl-CoA dehydrogenase and adipocyte protein 2. In addition, ID1216 increased the expression of adipose triglyceride lipase. These results suggest that ID1216 has anti-obesity effects by regulating the genes involved thermogenesis, ${\beta}$-oxidation and lipolysis in a diet-induced obesity model.

황정 주정 추출물 ID1216의 고지방 식이 유도 비만 마우스에서의 체중 증가 억제 효과에 대한 분자생물학적 기전을 확인하고자 단백질과 mRNA 수준에서 지질 및 에너지 대사 관련 유전자들의 발현 변화를 관찰하였다. 본 연구에서 확인된 지표들 간의 상호 작용 및 ID1216의 조절 여부에 관해 Fig. 10에 나타내었다. 실험 결과 ID1216은 고지방 식이 유도 비만 마우스에서 체중 증가 억제를 나타내었으며, 비만 대사 관련 pathway의 상위 유전자로 사료되는 SIRT1과 AMPK의 발현을 조절하는 것으로 나타났다. 활성화된 SIRT1과 AMPK는 $PGC1{\alpha}$의 활성화에 관여하고, 이를 통해 열 발산 대사와 관련된 UCP 단백질과 핵 수용체 단백질인 $PPAR{\alpha}$의 발현이 백색지방, 갈색지방, 간 및 근육에서 증가되는 것이 확인되었다. 각 조직 별로 RT-PCR을 진행한 결과에서는 $PPAR{\alpha}$의 하위 유전자인 aP2, ACO, Acadl, Acadm, CPT1a, CPT1b의 mRNA 발현 수준을 향상시켜 주어 ID1216이 지방산 산화 대사인 ${\beta}$-oxidation의 활성화에 기여할 가능성을 보여주었다. 이와는 별개로 ID1216은 중성지질을 분해하는 것으로 알려진 ATGL의 mRNA 발현 또한 증가시키는 것으로 확인되었다. 본 연구를 통해 ID1216이 조직에 따라 지질 및 에너지 대사와 관련된 인자의 발현에 영향을 주는 체중 조절에 효과적인 소재임을 알 수 있었다. 또한 비만 치료제와의 기전적 차별성과 생약 특유의 섭취 안전성을 특징으로 하는 체중 또는 체지방 조절 기능성 소재로의 활용 가능성도 충분히 가지고 있음을 확인할 수 있었다.

Keywords

References

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