title: 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.
abstract: 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 PPARgamma2-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.
authors.affiliation: School of Agricultural Biotechnology, Seoul National University, Seoul, South Korea.
authors.forename: Hyun-Seuk
authors.initials: HS
authors.lastname: Moon
authors.forename: Hong-Gu
authors.initials: HG
authors.lastname: Lee
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Seo
authors.forename: Ding-Ding
authors.initials: DD
authors.lastname: Guo
authors.forename: In-Yong
authors.initials: IY
authors.lastname: Kim
authors.forename: Chung-Soo
authors.initials: CS
authors.lastname: Chung
authors.forename: Tae-Gyu
authors.initials: TG
authors.lastname: Kim
authors.forename: Yun-Jaie
authors.initials: YJ
authors.lastname: Choi
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
mesh_terms: D041721:3T3-L1 Cells; D000067956:Adenylyl Cyclase Inhibitors; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D054392:Adipokines / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002250:Carbon Radioisotopes / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism*; D016048:Dideoxyadenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D005990:Glycerol / Q000032:analysis / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008970:Molecular Weight; D009570:Nitriles / Q000494:pharmacology; D019301:Oleic Acid / Q000032:analysis / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D012235:Rhodamines; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D054392:Adipokines; D002070:Butadienes; D002250:Carbon Radioisotopes; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D044243:Linoleic Acids, Conjugated; D009570:Nitriles; D012235:Rhodamines; C113580:U 0126; D019301:Oleic Acid; D011092:Polyethylene Glycols; D016048:Dideoxyadenosine; C021008:2',5'-dideoxyadenosine; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D016650:Fluorescein-5-isothiocyanate; D007545:Isoproterenol; D005990:Glycerol