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Lipolysis is stimulated by PEGylated conjugated linoleic acid through the cyclic adenosine monophosphate‐independent signaling pathway in 3T3‐L1 cells: Activation of MEK/ERK MAPK signaling pathway and hyper‐secretion of adipo‐cytokines
Author(s) -
Moon HyunSeuk,
Lee HongGu,
Seo JiHye,
Guo DingDing,
Kim InYong,
Chung ChungSoo,
Kim TaeGyu,
Choi YunJaie,
Cho ChongSu
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21219
Subject(s) - lipolysis , mapk/erk pathway , protein kinase a , conjugated linoleic acid , kinase , cyclic adenosine monophosphate , signal transduction , adenylyl cyclase , chemistry , medicine , endocrinology , biology , biochemistry , linoleic acid , adipose tissue , fatty acid , receptor
We previously reported that PEGylated conjugated linoleic acid (PCLA) as a pro‐drug treatment of cultures of 3T3‐L1 cells containing differentiated adipocytes caused de‐differentiation by downregulation of PPARγ2‐induced adipogenesis, and cell apoptosis induced by PCLA was lower than that induced by conjugated linoleic acid (CLA) owing to the biocompatible and hydrophilic properties of poly(ethylene glycol) (PEG). To further investigate our previous observations, the present study is designed to evaluate the lipolytic action of PCLA and its role in biochemical signaling pathways of 3T3‐L1 cells when compared to the CLA itself. Although both CLA and PCLA stimulated lipolysis, our results indicated a sensitivity difference between CLA and PCLA treatment: a time‐dependent effect on lipolysis and p‐extracellular signal‐related kinases (ERK) expression was observed for PCLA‐treated, but not for CLA‐treated cultures. Also, the induction by PCLA of mitogen‐activated protein kinase kinase (MEK)/ERK mitogen‐activated protein kinase (MAPK) activation was linked to secretion of adipo‐cytokines, interleukin‐6 (IL‐6), and interleukin‐8 (IL‐8), in time‐dependent manners. Interestingly, adenylyl cyclase inhibitor, 2′, 5′‐dideoxyadenosine (DDA), pre‐treatment did not prevent PCLA‐stimulated lipolysis. In fact, isoproterenol, but not PCLA, caused a significant increase in cyclic adenosine monophosphate (cAMP) levels, suggesting that the PCLA‐induced lipolysis was not mediated in the conventional cAMP‐dependent pathway and the cAMP was the intracellular mediator for isoproterenol‐induced lipolysis. Overall, our findings provide support for a role for PCLA as a pro‐drug in the regulation of metabolism in adipose tissue. J. Cell. Physiol. 214: 283–294, 2008. © 2007 Wiley‐Liss, Inc.