J. Lipid Res.
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A more recent version of this article appeared on March 1, 2008

Papers In Press, published online ahead of print December 4, 2007
J. Lipid Res., doi:10.1194/jlr.M700275-JLR200
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Submitted on June 13, 2007
Revised on November 7, 2007
Accepted on December 3, 2007

The trans-10, cis-12 Isomer of conjugated linoleic acid decreases adiponectin assembly by PPARgamma -dependent and PPARgamma -independent mechanisms

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

Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia B3H 1X8

Corresponding Author: 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 in mice and adipocyte cell culture models. The aim of this study was to determine if the effects of t-10, c-12 CLA on adiponectin and triglyceride are mediated through modulation of the transcription factor peroxisome proliferator-activated receptor  (PPAR). 3T3-L1 cells were treated either during or following differentiation into adipocytes with 100 M t-10, c-12 CLA with or without 10 M troglitazone, a PPAR agonist, or 1 M GW9662, a PPAR antagonist, and adiponectin and triglyceride levels were analyzed. Treatment with t-10, c-12 CLA reduced triglyceride as well as cellular and secreted adiponectin levels and impaired assembly of adiponectin oligomers. These changes were accompanied by decreases in PPAR mass. Troglitazone was able to reverse the t-10, c-12 CLA-mediated decrease in triglyceride levels and restore the assembly of adiponectin oligomers but was unable to restore adiponectin synthesis. Conversely, treatment with GW9662 decreased triglyceride 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 agonist and prevented stimulation of reporter activity by troglitazone. Therefore, the t-10, c-12 CLA isomer appears to alter adipocyte adiponectin metabolism through PPAR-dependent and PPAR-independent mechanisms.


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