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

• Published in: Archives of pharmacal research Vol. 36; no. 12; pp. 1541 - 1551
• Main Authors: Huang, Chia-Hsin, Shiu, Shin-Mau, Wu, Min-Tze, Chen, Wei-Lu, Wang, Shyang-Guang, Lee, Horng-Mo
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.12.2013; 대한약학회
• Subjects: acetyl-CoA carboxylase; AMP-activated protein kinase; AMP-Activated Protein Kinases - metabolism; Anticholesteremic Agents - pharmacology; Cell Survival - drug effects; Cell Survival - physiology; cholesterol; Dose-Response Relationship, Drug; fatty-acid synthase; Hep G2 Cells; human cell lines; Humans; lipid content; lipid metabolism; Lipid Metabolism - drug effects; Lipid Metabolism - physiology; lovastatin; Lovastatin - pharmacology; Medicine; Monascus; nicotinamide; Pharmacology/Toxicology; Pharmacy; phosphorylation; protein synthesis; Research Article; secondary metabolites; Signal Transduction - drug effects; Signal Transduction - physiology; Sirtuin 1 - metabolism; triacylglycerol lipase; Western blotting; 약학; AMPK; Monacolin K; Statin; SIRT1; Lipid; FoxO1
• ISSN: 0253-6269; 1976-3786; 1976-3786
• DOI: 10.1007/s12272-013-0150-2

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.