Signaling pathway of magnolol-stimulated lipolysis in sterol ester-loaded 3T3-L1 preadipocyes.
The aims of the present study were to examine the effect of magnolol on lipolysis in sterol ester (SE)-loaded 3T3-L1 preadipocytes and to determine the signaling mechanism involved. We demonstrate that magnolol treatment resulted in a decreased number and surface area of lipid droplets, accompanied by release of glycerol. The lipolytic effect of magnolol was not mediated by PKA based on the facts that magnolol did not induce an elevation of intracellular cAMP levels, and protein kinase A (PKA) inhibitor KT5720 did not block magnolol-induced lipolysis. Calcium/calmodulin-dependent protein kinase (CaMK) was involved in this signaling pathway, since magnolol-induced a transient rise of intracellular [Ca(2+)] and Ca(2+) influx across the plasma membrane, and CaMK inhibitor significantly abolished magnolol-induced lipolysis. Moreover, magnolol increased the relative levels of phosphorylated extracellular signal-related kinases (ERK1 and ERK2). In support of the involvement ERK, we demonstrated that magnolol-induced lipolysis was inhibited by PD98059, an inhibitor of mitogen-activated protein kinase kinase (MEK), and PD98059 reversed magnolol-induced ERK phosphorylation. Further, the relationship between CaMK and ERK was connected by the finding that CaMK inhibitor also blocked magnolol-induced ERK phosphorylation. Taken together, these findings suggest that magnolol-induced lipolysis is both CaMK- and ERK-dependent, and this lipolysis signaling pathway is distinct from the traditional PKA pathway. ERK phosphorylation is reported to enhance lipolysis by direct activation of hormone sensitive lipase (HSL), thus magnolol may likely activate HSL through ERK and increase lipolysis of adipocytes.
Huang
Shih-Horng
SH
Far Eastern Memorial Hospital, Department of Surgery and Division of General Surgery, Taipei, Taiwan.
Shen
Wung-Jing
WJ
Yeo
Hui-Lin
HL
Wang
Seu-Mei
SM
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005419:Flavonoids / Q000494:pharmacology; D005990:Glycerol / Q000032:analysis / Q000378:metabolism; D006888:Hydroxycholesterols / Q000378:metabolism / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D017705:Lignans / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D019301:Oleic Acid / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism; D000096926:Benzenesulfonamides
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001596:Benzylamines; D001713:Biphenyl Compounds; D002118:Calcium; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002227:Carbazoles; D017868:Cyclic AMP-Dependent Protein Kinases; D005419:Flavonoids; D005990:Glycerol; D006888:Hydroxycholesterols; D007211:Indoles; D017705:Lignans; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D009281:Naphthalenes; D019301:Oleic Acid; D011493:Protein Kinase C; D011758:Pyrroles; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate; C005498:magnolol; C072105:KN 93; D000096926:Benzenesulfonamides; C057416:KT 5720; C063302:KN 62; C007997:25-hydroxycholesterol; C058819:calphostin C; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one