title: Beneficial effects of beta-sitosterol on glucose and lipid metabolism in L6 myotube cells are mediated by AMP-activated protein kinase.
abstract: AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that has been implicated as a key factor for controlling intracellular lipids and glucose metabolism. Beta-sitosterol, a plant sterol known to prevent cardiovascular disease was identified from Schizonepeta tenuifolia to an AMPK activator. In L6 myotube cells, beta-sitosterol significantly increased phosphorylation of the AMPKalpha subunit and acetyl-CoA carboxylase (ACC) with stimulating glucose uptake. In contrast, beta-sitosterol treatment reduced intracellular levels of triglycerides and cholesterol in L6 cells. These effects were all reversed by pretreatment with AMPK inhibitor Compound C or LKB1 destabilizer radicicol. Similarly, beta-sitosterol-induced phosphorylation of AMPK and ACC was not increased in HeLa cells lacking LKB1. These results together suggest that beta-sitosterol-mediated enhancement of glucose uptake and reduction of triglycerides and cholesterol in L6 cells is predominantly accomplished by LKB1-mediated AMPK activation. Our findings further reveal a molecular mechanism underlying the beneficial effects of beta-sitosterol on glucose and lipid metabolism.
authors.affiliation: TG Biotech Research Institute, Technobuilding, Kyungpook National University, Daegu 702-831, Republic of Korea.
authors.forename: Seung-Lark
authors.initials: SL
authors.lastname: Hwang
authors.forename: Ha-Na
authors.initials: HN
authors.lastname: Kim
authors.forename: Hyun-Hee
authors.initials: HH
authors.lastname: Jung
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Choi
authors.forename: Jong-Moon
authors.initials: JM
authors.lastname: Hur
authors.forename: Jai-Youl
authors.initials: JY
authors.lastname: Lee
authors.forename: Hebok
authors.initials: H
authors.lastname: Song
authors.forename: Kyung-Sik
authors.initials: KS
authors.lastname: Song
authors.forename: Tae-Lin
authors.initials: TL
authors.lastname: Huh
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D012855:Sitosterols / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D051275:Glucose Transporter Type 4; D000960:Hypolipidemic Agents; D012855:Sitosterols; D014280:Triglycerides; C025473:gamma-sitosterol; D002784:Cholesterol; D017346:Protein Serine-Threonine Kinases; C488755:Stk11 protein, rat; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose