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

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 g (PPARg). 3T3-L1 cells were treated either during or after differentiation into adipocytes with 100 mM t-10, c-12 CLA with or without 10 mM troglitazone, a PPARg agonist, or 1 mM GW9662, a PPARg 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 PPARg 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 PPARg 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 PPARg-dependent and PPARgindependent mechanisms.-Miller, J. R., 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 PPARg-dependent and PPARgindependent mechanisms. J. Lipid Res. 2008. 49: 550-562.

Luteolin enhances insulin sensitivity via activation of PPARγ transcriptional activity in adipocytes

“…Activation of PPARγ by TZD induces adiponectin gene expression in 3T3-L1 adipocytes [22], while PPARγ activation has an inverse correlation with leptin gene expression, as reported in previous studies [30][31][32][33]. GW9662 is known as a potent and selective PPARγ antagonist and has been used to specifically block PPARγ activation in many studies [34][35][36]. Although it has also been reported that GW9662 might act through other PPARγ-independent pathways, selectively antagonizing PPARγ activity is the primary action of GW9662 [37].…”

Effects of Dietary Thiazolidinedione Supplementation on Growth Performance, Intramuscular Fat and Related Genes mRNA Abundance in the Longissimus Dorsi Muscle of Finishing Pigs

“…Conjugated linoleic acid (CLA) and Arginine (Arg) are two typical agents of this kind commonly used in the livestock industry. Previous studies have reported CLA can decrease the body fat mass (West et al, 1998; Sisk et al 2001; Meadus et al, 2002) and increase the lean body mass (House et al, 2005; Gaullier et al, 2007) through suppressing the expression of PPARγ (Kang et al, 2003), inhibiting the convertion of preadipocyte into adipocyte (Miller et al, 2008). Arg has also been reported to have the capacity to decrease the body fat accretion and enhance the muscle gain (He et al, 2009; Tan et al, 2009), which involves multiple NO-dependent pathways (Jobgen et al, 2006), and also correlated to the functions of PPARγ (Vasilijevic et al, 2010).…”

Dietary conjugated linoleic acid influences the content of stearinic acid in porcine adipose tissu

“…CLA inhibits adipogenesis -the conversion of preadipocytes into adipocytes involves the activation of key transcription factors such as peroxisome proliferator-activated receptor γ (PPARγ) and CAAT/enhancer binding protein (C/EBP). There is evidence that CLA suppresses preadipocyte differentiation in animals (Di Giancamillo et al 2007;Miller et al 2008) and humans (Brown et al 2004) preadipocytes. CLA increases inflammation -although the primary function of white adipose tissue is energy storage, it also has the ability to produce a number of proinflammatory cytokines.…”