Monacolin K affects lipid metabolism through SIRT1/AMPK pathway in HepG2 cells

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• 作者：Chia-Hsin Huang (1) (5)
  Shin-Mau Shiu (3)
  Min-Tze Wu (5)
  Wei-Lu Chen (4)
  Shyang-Guang Wang (2) (3)
  Horng-Mo Lee (2) (3) (4)
  
• 关键词：Monacolin K ; SIRT1 ; AMPK ; Statin ; FoxO1 ; Lipid
• 刊名：Archives of Pharmacal Research
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：36
• 期：12
• 页码：1541-1551
• 全文大小：
• 作者单位：Chia-Hsin Huang (1) (5)
  Shin-Mau Shiu (3)
  Min-Tze Wu (5)
  Wei-Lu Chen (4)
  Shyang-Guang Wang (2) (3)
  Horng-Mo Lee (2) (3) (4)
  
  1. Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan
  5. Agricultural Research Institute, Council of Agriculture, Executive Yuan, Taipei, Taiwan
  3. Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan
  4. Department of Medical Laboratory Science and Biotechnology, School of Medicine, Taipei Medical University, Taipei, Taiwan
  2. Institute of Pharmaceutical Science and Technology, Central Taiwan University of Science and Technology, No. 666, Buzih Road, Beitun District, Taichung, 40601, Taiwan
  
• ISSN：1976-3786

文摘

Monacolin K is the secondary metabolite isolated from Monascus spp. It is the natural form of lovastatin, which is clinically used to reduce the synthesis of cholesterol by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase. In the present study, monacolin K increased protein expression of SIRT1 and phosphorylation level of AMP-activated protein kinase (AMPK) in HepG2 cells. Through activation of SIRT1/AMPK pathway, monacolin K increased phosphorylation of acetyl CoA carboxylase and caused nuclear translocation of forkhead box O1. The western blotting results showed that monacolin K increased expression of adipose triglyceride lipase but decreased abundances of fatty acid synthase (FAS) and sterol regulatory element-binding protein 1 (SREBP1). Monacolin K also decreased the intracellular accumulation of lipids as demonstrated by Oil Red O staining. In addition, the immunostaining showed that monacolin K prevented the nuclear translocation of SREBP1, indicating the association with down-regulation of FAS. All the demonstrated effects of monacolin K were counteracted by nicotinamide or compound C, the inhibitors of SIRT1 or AMPK. In summary, monacolin K reduces the lipid content through SIRT1/AMPK pathway in HepG2 cells, which promotes catabolism and inhibits anabolism of lipid.