Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
권호 표지
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Effects of Piperine on Insulin Resistance and Lipid Accumulation in Palmitate-treated HepG2 Cells

Palmitate처리된 인간 간세포주 HepG2 세포에서 piperine의 지질 축적과 인슐린 저항성 기전에 대한 연구

  • Jung, Hee Jin (Longevity Life Science and Technology Institutes, Pusan National University) ;
  • Bang, EunJin (Department of Pharmacy, College of Pharmacy, Pusan National University) ;
  • Jeong, Seong Ho (Department of Pharmacy, College of Pharmacy, Pusan National University) ;
  • Kim, Byeong Moo (Department of Pharmacy, College of Pharmacy, Pusan National University) ;
  • Chung, Hae Young (Longevity Life Science and Technology Institutes, Pusan National University)
  • 정희진 (부산대학교 장수생명과학기술연구원) ;
  • 방은진 (부산대학교 약학대학 약학과) ;
  • 정성호 (부산대학교 약학대학 약학과) ;
  • 김병무 (부산대학교 약학대학 약학과) ;
  • 정해영 (부산대학교 장수생명과학기술연구원)
  • Received : 2019.09.03
  • Accepted : 2019.09.23
  • Published : 2019.09.30
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Abstract

Hepatic lipid accumulation and insulin resistance increases in patients with non-alcoholic fatty liver disease. Piperine is a major compound found in black pepper (Piper nigrum) and long pepper (P. longum). Piperine has been used in fine chemical for its anti-cancer, anti-obesity, anti-diabetic, anti-inflammatory and anti-oxidant properties. However, the signaling-based mechanism of piperine and its role as an inhibitor of lipogenesis and insulin resistance in human hepatocyte cells remains ill-defined. In the present study, we explored the effects of piperine on lipid accumulation and insulin resistance, and explored the potential underlying molecular mechanisms in palmitate-treated HepG2 cells. Piperine treatment resulted in a significant reduction of triglyceride content. Furthermore, piperine treatment decreased palmitate-treated intracellular lipid deposition by inhibiting the lipogenic target genes, sterol-regulatory-element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS); whereas the expression of carnitine palmitoyl transferase (CPT-1) and phosphorylation of acetyl coenzyme A carboxylase (ACC) gene involved in fatty acid oxidation was increased. Moreover, piperine also inhibited the phosphorylation of insulin receptor substrate (IRS)-1 (Ser307). Piperine treatment modulated palmitate-treated lipid accumulation and insulin resistance in HepG2 cells with concomitant reduction of lipogenic target genes, such as SREBP-1 and FAS, and induction of CPT-1-ACC and phosphorylation of IRS-1 (Tyr632)-Akt pathways. Therefore, piperine represents a promising treatment for the prevention of lipid accumulation and insulin resistance.

간의 지질 축적과 인슐린 저항성은 비알콜성 지방간 환자에게서 증가한다. Piperine은 후추(Piper nigrum)와 필발(인도산 후추, P. longum)의 주요 성분으로 항암, 항비만, 항 당뇨병, 항염증 및 항산화 등의 생리활성이 보고되었다. 그러나 piperine의 인간 간세포 HepG2 세포에서 지질 축적과 인슐린 저항성의 억제제로서의 연구는 보고된 바가 없다. 본 연구의 목적은 지질 축적 및 인슐린 저항성에 대한 piperine의 효과를 palmitate처리된 HepG2 세포에서 잠재적인 분자 기전을 밝히는 것이다. 그 결과 piperine처리군은 지질 함량을 감소시켰고, 지방 형성 표적 유전자인 SREBP-1c와 FAS의 발현을 억제함으로써 palmitate처리된 세포내 지질 축적을 감소시켰다. 게다가 piperine처리군은 지방산 산화에 관련된 CPT-1과 인산화된 ACC 및 인산화된 IRS-1 (Tyr632)와 Akt의 레벨을 증가시켰다. 또한, piperine처리군은 인산화된 IRS-1 (Ser307)의 레벨을 감소시켰다. 결론적으로 palmitate처리된 HepG2 세포에서 piperine은 SREBP-1와 FAS발현의 감소 및 CPT-1과 ACC 인산화의 증가 및 인산화된 IRS-1(Try632)와 Akt 신호전달 경로를 조절함으로써 지질 축적 및 인슐린 저항성을 개선함을 확인하였다. 따라서 piperine의 지질 축적 및 인슐린 저항성을 예방하는 약물로써 가능성이 제시되었다.

Keywords

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