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

Hyun-Seuk Moon, Hong Gu Lee, Ji Hye Seo, Ding Ding Guo, In Yong Kim, Chung Soo Chung, Tae Gyu Kim, Yun Jaie Choi, Chong Su Cho

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

We previously reported that PEGylated conjugated linoleic acid (PCLA) as a pro-drug treatment of cultures of 3T3-LI 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-LI 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.

Original languageEnglish
Pages (from-to)283-294
Number of pages12
JournalJournal of Cellular Physiology
Volume214
Issue number2
DOIs
Publication statusPublished - 2008 Feb 1
Externally publishedYes

Fingerprint

3T3-L1 Cells
Conjugated Linoleic Acids
Lipolysis
Secretory Pathway
Mitogen-Activated Protein Kinase Kinases
Mitogen-Activated Protein Kinases
Cyclic AMP
Phosphotransferases
Chemical activation
Cytokines
3T3 Cells
Prodrugs
Isoproterenol
Polyethylene glycols
Dideoxyadenosine
Drug therapy
Adipogenesis
Ethylene Glycol
Drug and Narcotic Control

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

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. / Moon, Hyun-Seuk; Lee, Hong Gu; Seo, Ji Hye; Guo, Ding Ding; Kim, In Yong; Chung, Chung Soo; Kim, Tae Gyu; Choi, Yun Jaie; Cho, Chong Su.

In: Journal of Cellular Physiology, Vol. 214, No. 2, 01.02.2008, p. 283-294.

Research output: Contribution to journalArticle

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abstract = "We previously reported that PEGylated conjugated linoleic acid (PCLA) as a pro-drug treatment of cultures of 3T3-LI 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-LI 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.",
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AU - Moon, Hyun-Seuk

AU - Lee, Hong Gu

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AU - Kim, In Yong

AU - Chung, Chung Soo

AU - Kim, Tae Gyu

AU - Choi, Yun Jaie

AU - Cho, Chong Su

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