title: Monacolin K affects lipid metabolism through SIRT1/AMPK pathway in HepG2 cells.
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.
authors: Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan.
authors: Chia-Hsin
authors: CH
authors: Huang
authors: Shin-Mau
authors: SM
authors: Shiu
authors: Min-Tze
authors: MT
authors: Wu
authors: Wei-Lu
authors: WL
authors: Chen
authors: Shyang-Guang
authors: SG
authors: Wang
authors: Horng-Mo
authors: HM
authors: Lee
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology*; D008148:Lovastatin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D000924:Anticholesteremic Agents; D008148:Lovastatin; D055372:AMP-Activated Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1