Conjugated linoleic acid regulates phosphorylation of PPARγ by modulation of ERK 1/2 and p38 signaling in human macrophages/fatty acid-laden macrophages

Stimulation of macrophages by a variety fatty acids causes activation of MAP kinases (MAPKs). The consequences arising from down-regulation of MAPKs may be a limitation in the activity of PPARγ, which is modulated by a modification catalyzed by these kinases. Phosphorylation of MAP kinases-ERK1/2 and p38 as well as PPARγ was determined by real-time polymerase chain reaction and Western blotting in human macrophages cultured with conjugated linoleic acids (CLAs). We demonstrated that CLA isomers alter MAP kinase phosphorylation and PPARγ activation. Phosphorylation of ERK1/2 was diminished in cells cultivated with cis-9,trans-11 CLA, whereas phosphorylation of p38 was reduced by trans-10,cis-12 CLA. PPARγ was phosphorylated mainly by ERK1/2, and consequently, PPARγ phosphorylation was suppressed mainly by cis-9,trans-11 isomer. In human adipocytes, cis-9,trans-11 C 18:2 raised the activation of PPAR and several of its downstream target genes. We suggest that a similar process may also occur in human macrophages.     

Effects of polyphenolic compounds on tumor necrosis factor-α (TNF-α)-induced changes of adipokines and oxidative stress in 3T3-L1 adipocytes

Over the last few decades, obesity has become a global epidemic in both developed and developing countries. Recent studies have indicated that obesity is closely associated with chronic inflammation characterized by abnormal levels of adipocytokines and inflammatory cytokines in adipocytes. The aim of this work was to study the effects of 21 polyphenolic compounds on tumor necrosis factor-α (TNF-α)-induced changes of adipokines and oxidative stress in 3T3-L1 adipocytes. The results showed that p-coumaric acid, quercetin, and resveratrol have greater inhibition (p < 0.05) of a TNF-α-induced increase in the production of interleukin-6 (IL-6) among 21 tested polyphenolic compounds. p-Coumaric acid, quercetin, and resveratrol demonstrated inhibitions of TNF-α-induced changes in levels of monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1), and intracellular reactive oxygen species (ROS) in 3T3-L1 adipocytes. Furthermore, p-coumaric acid, quercetin, and resveratrol increased levels (p < 0.05) of secreted adiponectin, superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and glutathione S-transferase (GST) in TNF-α-treated 3T3-L1 adipocytes. These results indicate that the inhibition of TNF-α-induced changes of adipokines and oxidative stress by some polyphenolic compounds might have further implications in preventing obesity-related pathologies.