J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M700275-JLR200 on December 4, 2007

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Journal of Lipid Research, Vol. 49, 550-562, March 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

The trans-10, cis-12 isomer of conjugated linoleic acid decreases adiponectin assembly by PPAR{gamma}-dependent and PPAR{gamma}-independent mechanisms

Jessica R. Miller, Pilaiwan Siripurkpong, Jennifer Hawes, Amin Majdalawieh1, Hyo-Sung Ro and Roger S. McLeod2

Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1X5

Published, JLR Papers in Press, December 4, 2007.

1 Present address of A. Majdalawieh: Department of Biology and Chemistry, American University of Sharjah, Sharjah, United Arab Emirates.

2 To whom correspondence should be addressed. e-mail: rmcleod2{at}dal.ca

The adipocyte-derived secretory protein adiponectin functions as an insulin-sensitizing agent. In plasma, adiponectin exists as low, medium, and high molecular weight oligomers. Treatment with trans-10, cis-12 conjugated linoleic acid (t-10, c-12 CLA) reduces levels of adiponectin as well as triglyceride (TG) in mice and adipocyte cell culture models. The aim of this study was to determine whether the effects of t-10, c-12 CLA on adiponectin and TG are mediated through modulation of the transcription factor peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}). 3T3-L1 cells were treated either during or after differentiation into adipocytes with 100 µM t-10, c-12 CLA with or without 10 µM troglitazone, a PPAR{gamma} agonist, or 1 µM GW9662, a PPAR{gamma} antagonist, and adiponectin and TG levels were analyzed. Treatment with t-10, c-12 CLA reduced TG as well as cellular and secreted adiponectin levels and impaired the assembly of adiponectin oligomers. These changes were accompanied by decreases in PPAR{gamma} mass. Troglitazone was able to reverse the t-10, c-12 CLA-mediated decrease in TG levels and restore the assembly of adiponectin oligomers but was unable to restore adiponectin synthesis. Conversely, treatment with GW9662 decreased TG mass and impaired adiponectin oligomer assembly but did not decrease total adiponectin mass. In a reporter assay, t-10, c-12 CLA appeared to be a partial PPAR{gamma} agonist and prevented the stimulation of reporter activity by troglitazone. Therefore, the t-10, c-12 CLA isomer appears to alter adipocyte adiponectin metabolism through PPAR{gamma}-dependent and PPAR{gamma}-independent mechanisms.

Supplementary key words mouse • 3T3-L1 • adipocyte • peroxisome proliferator-activated receptor {gamma}


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