title: Phillyrin attenuates high glucose-induced lipid accumulation in human HepG2 hepatocytes through the activation of LKB1/AMP-activated protein kinase-dependent signalling.
abstract: Phillyrin, an active constituent found in many medicinal plants and certain functional foods, has anti-obesity activity in vivo. The aim of our study was to provide new data on the molecular mechanism(s) underlying the role of phillyrin in the prevention of high glucose-induced lipid accumulation in human HepG2 hepatocytes. We found that phillyrin suppressed high glucose-induced lipid accumulation in HepG2 cells. Phillyrin strongly inhibited high glucose-induced fatty acid synthase (FAS) expression by modulating sterol regulatory element-binding protein-1c (SREBP-1c) activation. Moreover, use of the pharmacological AMP-activated protein kinase (AMPK) inhibitor compound C revealed that AMPK is essential for suppressing SREBP-1c expression in phillyrin-treated cells. Finally, we found that liver kinase B1 (LKB1) phosphorylation is required for the phillyrin-enhanced activation of AMPK in HepG2 hepatocytes. These results indicate that phillyrin prevents lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and FAS through LKB1/AMPK activation, suggesting that phillyrin is a novel AMPK activator with a role in the prevention and treatment of obesity.
authors.affiliation: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea.
authors.forename: Minh Truong
authors.initials: MT
authors.lastname: Do
authors.forename: Hyung Gyun
authors.initials: HG
authors.lastname: Kim
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Tilak
authors.initials: T
authors.lastname: Khanal
authors.forename: Bong Hwan
authors.initials: BH
authors.lastname: Park
authors.forename: Thu Phuong
authors.initials: TP
authors.lastname: Tran
authors.forename: Yong Pil
authors.initials: YP
authors.lastname: Hwang
authors.forename: Minkyun
authors.initials: M
authors.lastname: Na
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005960:Glucosides / Q000494:pharmacology*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D005960:Glucosides; D010936:Plant Extracts; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose; C075528:phillyrin