Signaling Pathway of Magnolol-Stimulated Lipolysis in Sterol Ester-Loaded 3t3-L1 Preadipocyes
Resource
JOURNAL OF CELLULAR BIOCHEMISTRY v.91 n.5 pp.1021~1029
Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Journal Volume
v.91
Journal Issue
n.5
Pages
1021-1029
Date Issued
2004
Date
2004
Author(s)
Huang, Shih-Horng
Shen, Wung-Jing
Yeo, Hui-Lin
Wang, Seu-Mei
Abstract
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 rnagnolol 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 rnagnolol 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 [Ca2+] and Ca2+ influx across the plasma membrane, and CaMK inhibitor significantly abolished- magnolol-induced lipolysis. Moreover, rnagnolol increased the relative levels of phosphorylated extracellular signal- related kinases (ERK1 and ERK2). In Support of the involvement ERK, we demonstrated that rnagnolol-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. (C) 2004 Wilev-Liss, Inc
Subjects
sterol ester-loaded preadipocyte
lipolysis
magnolol
signaling pathway
Type
journal article