Recently it has become evident that obesity is associated with low grade chronic inflammation. The transcription factor PPAR has been shown to have a strong anti-inflammatory action in liver. However, the role of PPAR in obesity-induced inflammation is much less clear. Therefore, the aim of our study was to determine whether PPAR plays a role in obesity-induced hepatic inflammation.

To induce obesity, Wildtype sv129 and PPAR-/- mice were exposed to a chronic high fat diet (HFD), using a low fat diet (LFD) as control. In Wildtype mice, HFD significantly increased the hepatic and adipose expression of numerous genes involved in inflammation. Importantly, this effect was amplified in PPAR-/- mice, suggesting an anti-inflammatory role of PPAR in liver and adipose tissue. Further analysis identified specific chemokines and macrophage markers, including MCP-1 and F4/80+, that were elevated in liver and adipose tissue of PPAR-/- mice, indicating increased inflammatory cell recruitment in the knock-out animals. When all groups of mice were analyzed together, a significant correlation between hepatic TG and expression of inflammatory markers was observed. Many inflammatory genes that were up-regulated in PPAR-/- livers by HFD were down-regulated by treatment with the PPAR ligand Wy-14643 under normal non-steatotic conditions, either in vivo or in vitro, suggesting an anti-inflammatory effect of PPAR that is independent of reduction in liver TG.

In conclusion, our results suggest that PPAR protects against obesity-induced chronic inflammation in liver by reducing hepatic steatosis, by direct down-regulation of inflammatory genes, and by attenuating inflammation in adipose tissue.