Beneficial effects of beta-sitosterol on glucose and lipid metabolism in L6 myotube cells are mediated by AMP-activated protein kinase.
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.
Hwang
Seung-Lark
SL
TG Biotech Research Institute, Technobuilding, Kyungpook National University, Daegu 702-831, Republic of Korea.
Kim
Ha-Na
HN
Jung
Hyun-Hee
HH
Kim
Ji-Eun
JE
Choi
Dong-Kyu
DK
Hur
Jong-Moon
JM
Lee
Jai-Youl
JY
Song
Hebok
H
Song
Kyung-Sik
KS
Huh
Tae-Lin
TL
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
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