Endocrinology and Metabolism

The Korean Endocrine Society (대한내분비학회)
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Effects of Alpha-lipoic Acid on SREBP-1c Expression in HepG2 Cells

알파-리포산이 HepG2 간세포에서 SREBP-1c 발현에 미치는 효과

Yun, Tae-Sung;Min, Ae-Kyung;Kim, Nam-Kyung;Kim, Mi-Kyung;Cho, Ho-Chan;Kim, Hye-Soon;Hwang, Jae-Seok;Ryu, Seong-Yeol;Park, Keun-Gyu;Lee, In-Kyu
윤태승;민애경;김남경;김미경;조호찬;김혜순;황재석;류성열;박근규;이인규

  • Published : 2008.02.10
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Abstract

Background: Non-alcoholic fatty liver disease is common in patients with insulin resistance. Sterol regulatory element binding protein-1c (SREBP-1c) is a member of a family of transcription factors that have been recognized as key regulators for lipid accumulation in the liver that activate enzymes involved in the fatty acid biosynthetic pathway. This study was designed to evaluate whether alpha-lipoic acid (ALA) inhibits insulin-stimulated SREBP-1c expression.Methods: We investigated the effects of ALA on insulin-stimulated SREBP-1c expression in a human hepatoma cell line (HepG2 cells) using Northern and Western blot analysis. We also examined the effect of ALA on the promoter activity of the SREBP-1c gene to examine whether ALA can affect SREBP-1c expression at the transcriptional level. To discern the mechanism by which ALA inhibits SREBP-1c expression, we examined the role of AMP-activated protein kinase (AMPK). Results: Insulin increased the expression of SREBP-1c mRNA and protein in HepG2 cells in a dose depended manner. Co-treatment with ALA inhibited the insulin increased SREBP-1c expression in a dose-dependent manner. ALA also inhibited insulin-stimulated activation of the SREBP-1c promoter activity, indicating that ALA inhibited SREBP-1c expression at the transcriptional level. ALA increased phosphorylation of AMPK in HepG2 cells. Inhibition of the AMPK activity by compound C markedly reversed the inhibitory effects of ALA for insulin-stimulated SREBP-1c expression. These results suggest that ALA-induced suppression of SREBP-1c expression is at least in part mediated via AMPK activation.Conclusion: The present study suggests that ALA has an inhibitory effect on insulin-stimulated SREBP-1c expression. Therefore, further studies on the effects of ALA on hepatic steatosis in an animal model need to be performed. (J Kor Endocr Soc 23:27~34, 2008)

연구배경: 비알콜성 지방간은 인슐린 저항성이 있는 환자에서 흔히 발생 하는 간질환이다. SREBP-1c는 지방산의 생합성에 관여하는 효소를 활성화시켜서 간 내 지방 축적을 일으키는 중요한 전사조절인자이다. 본 연구는 알파-리포산이 간세포에서 인슐린에 의해 증가된 SREBP-1c 발현에 미치는 영향을 알아 보고자 하였다.방법: 간세포로 human hepatoma cell line인 HepG2 세포를 사용하였다. 인슐린과 알파-리포산이 SREBP-1c 발현에 미치는 영향을 노던 블롯과 웨스턴 블롯으로 확인하였다. SREBP-1c 전사조절부위(promoter)활성 분석을 통해 알파-리포산이 SREBP-1c의 전사조절에 관여하는지 알아보았다. 알파-리포산이 AMPK 활성에 미치는 효과는 AMPK의 인산화로 평가하였으며 AMPK 억제제인 compound C를 이용하여 알파-리포산의 억제효과가 AMPK를 통해 이루어지는지 알아보았다. 결과: 인슐린은 용량-의존적으로 HepG2 세포에서 SREBP-1c mRNA 및 단백질 발현을 증가시켰다. 알파-리포산은 인슐린에 의해 증가된 SREBP-1c의 발현을 억제하였다. 알파-리포산은 인슐린에 의해 증가된 SREBP-1c 전사촉진자의 활성을 억제하였다. 알파-리포산은 HepG2 세포에서 AMPK의 인산화를 증가시켰다. AMPK 활성 억제제인 compound C는 알파-리포산에 의한 SREBP-1c 발현 억제효과를 의미 있게 회복시켰다.

Keywords

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