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.

Dietary Conjugated Linoleic Acid Induces Lipolysis in Adipose Tissue of Coconut Oil‐Fed Mice but not Soy Oil‐Fed Mice

“…Also it has been shown in previous studies that dietary CLA causes a reduction in both epididymal and retroperitoneal fat pad weights [10]. Several studies have shown that CLA causes an increase in lipolysis [13,14], while others have reported no effect of CLA on lipolysis [29][30][31]. The responses to CLA tended to be observed in cells that had been cultured in serum-free media [13,14].…”

“…Several studies have shown that CLA causes an increase in lipolysis [13,14], while others have reported no effect of CLA on lipolysis [29][30][31]. The responses to CLA tended to be observed in cells that had been cultured in serum-free media [13,14]. Serum starving makes the cultures devoid of fatty acids that could potentially interfere with CLA.…”

“…The mechanism behind the enhanced response with CO feeding is not yet known. However, several cell culture studies have reported that CLA supplementation causes an increase in lipolysis [13,14]. Coconut oil is composed mainly of medium chain saturated fatty acids hence it is likely that they would undergo oxidation more rapidly as compared to the longer chain and unsaturated fatty acids present in soy oil diets [15,16].…”

Identification and Saturable Nature of Signaling Pathways Induced by Metreleptin in Humans: Comparative Evaluation of In Vivo, Ex Vivo, and In Vitro Administration

“…Lipolysis assay was performed using [ 14 C]oleic acid method (22). In brief, the cells were seeded on 12-well culture plates.…”

Adipocytes Differentiated In Vitro from Rat Mesenchymal Stem Cells Lack Essential Free Fatty Acids Compared to Adult Adipocytes

“…Conjugated linoleic acid induced human adipocyte delipidation [9]. PEGylated linoleic acid stimulated lipolysis in 3T3-L1 cells [10] and activated the integrated stress response pathway in adipocytes [11]. When administered in a diet, linoleic acid reduced adipocyte size and changed the secretion of adipokines in obese rats [12]; in rat adipocytes linoleic acid influenced the secretion of leptin and adiponectin and its dietary intake reduced body fat in animals and some humans [13].…”