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

Chia Hsin Huang, Shin Mau Shiu, Min Tze Wu, Wei Lu Chen, Shyang Guang Wang, Horng Mo Lee

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1541-1551
Number of pages11
JournalArchives of Pharmacal Research
Volume36
Issue number12
DOIs
Publication statusPublished - Dec 2013

Keywords

  • AMPK
  • FoxO1
  • Lipid
  • Monacolin K
  • SIRT1
  • Statin

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine
  • Organic Chemistry

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  • Cite this

    Huang, C. H., Shiu, S. M., Wu, M. T., Chen, W. L., Wang, S. G., & Lee, H. M. (2013). Monacolin K affects lipid metabolism through SIRT1/AMPK pathway in HepG2 cells. Archives of Pharmacal Research, 36(12), 1541-1551. https://doi.org/10.1007/s12272-013-0150-2