Abstract
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 (PPARgamma). 3T3-L1 cells were treated either during or after differentiation into adipocytes with 100 microM t-10, c-12 CLA with or without 10 microM troglitazone, a PPARgamma agonist, or 1 microM GW9662, a PPARgamma 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 PPARgamma 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 PPARgamma 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 PPARgamma-dependent and PPARgamma-independent mechanisms.
Highlights
The adipocyte-derived secretory protein adiponectin functions as an insulin-sensitizing agent
We examined whether the t -10, c -12 Conjugated linoleic acid (CLA)-mediated reductions in TG and adiponectin mass occur through a peroxisome proliferator-activated receptor g (PPARg)-dependent mechanism by comparison with a known PPARg agonist, the TZD troglitazone, and a known PPARg antagonist, GW9662
In the presence of t -10, c -12 CLA, TG levels in 3T3L1 cells were reduced to one-quarter of the level in control cells without fatty acid (0.37 6 0.07 vs. 1.45 6 0.14 mg TG/mg cell protein; P, 0.01) or cells differentiated in the presence c -9, t -11 CLA (P, 0.01) (Fig. 1A)
Summary
The adipocyte-derived secretory protein adiponectin functions as an insulin-sensitizing agent. The t -10, c -12 CLA isomer has been shown to reduce obesity in animals [2,3,4,5,6,7,8] and triglyceride (TG) accumulation in adipocyte cell culture models [9,10,11,12], with its greatest effects, to date, having been shown in the mouse [13] This has led to the promotion of CLA as a weight-loss supplement in humans. Peroxisome proliferator-activated receptor g (PPARg) is an essential transcription factor in adipogenesis that induces the expression of the genes necessary for the acquisition and maintenance of the mature adipocyte phenotype These include LPL [17], the adipocyte fatty acid binding protein aP2 [18], and the glucose transport protein GLUT4 [19]. Ferentiated in the presence of individual CLA isomers, only treatment with t -10, c -12 CLA caused a marked reduction in the expression of PPARg as well as LPL, aP2, and GLUT4 [22]
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