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

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Lovastatin
AMP-Activated Protein Kinases
Hep G2 Cells
Lipid Metabolism
Sterol Regulatory Element Binding Protein 1
Fatty Acid Synthases
Phosphorylation
Lipids
Monascus
Acetyl-CoA Carboxylase
Niacinamide
Metabolites
Lipase
Oxidoreductases
Down-Regulation
Western Blotting
Chemical activation
Cholesterol
Association reactions
Staining and Labeling

Keywords

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

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine
  • Organic Chemistry

Cite this

Monacolin K affects lipid metabolism through SIRT1/AMPK pathway in HepG2 cells. / Huang, Chia Hsin; Shiu, Shin Mau; Wu, Min Tze; Chen, Wei Lu; Wang, Shyang Guang; Lee, Horng Mo.

In: Archives of Pharmacal Research, Vol. 36, No. 12, 12.2013, p. 1541-1551.

Research output: Contribution to journalArticle

Huang, Chia Hsin ; Shiu, Shin Mau ; Wu, Min Tze ; Chen, Wei Lu ; Wang, Shyang Guang ; Lee, Horng Mo. / Monacolin K affects lipid metabolism through SIRT1/AMPK pathway in HepG2 cells. In: Archives of Pharmacal Research. 2013 ; Vol. 36, No. 12. pp. 1541-1551.
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