HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M400476-JLR200v1 46/5/885    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chung, S. Articles by McIntosh, M. Search for Related Content PubMed PubMed Citation Articles by Chung, S. Articles by McIntosh, M. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 46, 885-895, May 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Trans-10,cis-12 CLA increases adipocyte lipolysis and alters lipid droplet-associated proteins: role of mTOR and ERK signaling

Soonkyu Chung^*, Jonathan Mark Brown, Maria Boysen Sandberg and Michael McIntosh^1,*

^* Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27402-6170
Department of Pathology and Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, DK-5230, Denmark

¹ To whom correspondence should be addressed. e-mail: mkmcinto{at}uncg.edu

Lipid droplet-associated proteins play an important role in adipocyte triglyceride (TG) metabolism. Here, we show that trans-10,cis-12 conjugated linoleic acid (CLA), but not cis-9,trans-11 CLA, increased lipolysis and altered human adipocyte lipid droplet morphology. Before this change in morphology, there was a rapid trans-10,cis-12 CLA-induced increase in the accumulation of perilipin A in the cytosol, followed by the disappearance of perilipin A protein. In contrast, protein levels of adipose differentiation-related protein (ADRP) were increased in cultures treated with trans-10,cis-12 CLA. Immunostaining revealed that ADRP localized to the surface of small lipid droplets, displacing perilipin. Intriguingly, trans-10,cis-12 CLA increased ADRP protein expression to a much greater extent than ADRP mRNA without affecting stability, suggesting translational control of ADRP. To this end, we found that trans-10,cis-12 CLA increased activation of the mammalian target of rapamycin/p70 S6 ribosomal protein kinase/S6 ribosomal protein (mTOR/p70S6K/S6) pathway.

Collectively, these data demonstrate that the trans-10,cis-12 CLA-mediated reduction of human adipocyte TG content is associated with the differential localization and expression of lipid droplet-associated proteins. This process involves both the translational control of ADRP through the activation of mTOR/p70S6K/S6 signaling and transcriptional control of perilipin A.

Abbreviations: ADRP, adipose differentiation-related protein; CLA, conjugated linoleic acid; ERK, extracellular signal-related kinase; GPCR, G protein-coupled receptor; HSL, hormone-sensitive lipase; MEK, mitogen-activated protein kinase kinase; mTOR, mammalian target of rapamycin; PKA, protein kinase A; p70S6K, p70 S6 ribosomal protein kinase; S6, S6 ribosomal protein; SV, stromal vascular; TG, triglyceride; TNF-, tumor necrosis factor-; UTR, untranslated region; 5'-TOP, 5'-terminal oligopyrimidine

Supplementary key words conjugated linoleic acid • perilipin • adipose differentiation-related protein • triglycerides • mammalian target of rapamycin • mitogen-activated protein kinase kinase/extracellular signal-related kinase signaling

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. R. Miller, P. Siripurkpong, J. Hawes, A. Majdalawieh, H.-S. Ro, and R. S. McLeod The trans-10, cis-12 isomer of conjugated linoleic acid decreases adiponectin assembly by PPAR{gamma}-dependent and PPAR{gamma}-independent mechanisms J. Lipid Res., March 1, 2008; 49(3): 550 - 562. [Abstract] [Full Text] [PDF]

				C. M. Maya-Monteiro, P. E. Almeida, H. D'Avila, A. S. Martins, A. P. Rezende, H. Castro-Faria-Neto, and P. T. Bozza Leptin Induces Macrophage Lipid Body Formation by a Phosphatidylinositol 3-Kinase- and Mammalian Target of Rapamycin-dependent Mechanism J. Biol. Chem., January 25, 2008; 283(4): 2203 - 2210. [Abstract] [Full Text] [PDF]

				P. C. LaRosa, J.-J. M. Riethoven, H. Chen, Y. Xia, Y. Zhou, M. Chen, J. Miner, and M. E. Fromm Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes Physiol Genomics, November 14, 2007; 31(3): 544 - 553. [Abstract] [Full Text] [PDF]

				P. C. LaRosa, J. Miner, Y. Xia, Y. Zhou, S. Kachman, and M. E. Fromm Trans-10, cis-12 conjugated linoleic acid causes inflammation and delipidation of white adipose tissue in mice: a microarray and histological analysis Physiol Genomics, November 21, 2006; 27(3): 282 - 294. [Abstract] [Full Text] [PDF]

				U. Edvardsson, A. Ljungberg, D. Linden, L. William-Olsson, H. Peilot-Sjogren, A. Ahnmark, and J. Oscarsson PPAR{alpha} activation increases triglyceride mass and adipose differentiation-related protein in hepatocytes J. Lipid Res., February 1, 2006; 47(2): 329 - 340. [Abstract] [Full Text] [PDF]

				S. Chung, J. M. Brown, J. N. Provo, R. Hopkins, and M. K. McIntosh Conjugated Linoleic Acid Promotes Human Adipocyte Insulin Resistance through NF{kappa}B-dependent Cytokine Production J. Biol. Chem., November 18, 2005; 280(46): 38445 - 38456. [Abstract] [Full Text] [PDF]