Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that play pivotal roles in the regulation of a very large number of biological processes including inflammation. Using specific examples, this paper focuses on the interplay between PPARs and innate immunity/inflammation and, when possible, compares it among species. We focus on recent discoveries establishing how inflammation and PPARs interact in the context of obesity-induced inflammation and type 2 diabetes, mostly in mouse and humans. We illustrate that PPARγ ability to alleviate obesity-associated inflammation raises an interesting pharmacologic potential. In the light of recent findings, the protective role of PPARα and PPARβ/δ against the hepatic inflammatory response is also addressed. While PPARs agonists are well-established agents that can treat numerous inflammatory issues in rodents and humans, surprisingly very little has been described in other species. We therefore also review the implication of PPARs in inflammatory bowel disease; acute-phase response; and central, cardiac, and endothelial inflammation and compare it along different species (mainly mouse, rat, human, and pig). In the light of the data available in the literature, there is no doubt that more studies concerning the impact of PPAR ligands in livestock should be undertaken because it may finally raise unconsidered health and sanitary benefits. 1. Introduction The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that play critical roles in very different biological pathways such as lipid, protein, glycerol, urea, glucose, glycogen and lipoprotein metabolism, adipogenesis, trophoblast differentiation, and cell migration [1–6]. Notably, PPARs are also required to balance cell proliferation and cell death and therefore impact skin wound healing and proliferative diseases such as cancer [7–9]. PPARs are also prominent players in inflammation control [10, 11]. PPARα, the first PPAR isotype identified in mouse, was originally cloned in the early 1990s as a novel member of the steroid hormone receptor superfamily [12]. Shortly after, a rat version of PPARα as well as three novel members related to each other (xPPARα, xPPARβ, and xPPARγ) and to mouse PPARα have been subsequently cloned from Xenopus (frog) [13]. Since then, substantial efforts have been made to identify other related receptors; several additional PPAR isoforms and variants have been therefore isolated in a wide range of species including mammals (human, rabbit, mouse, rat, pig,
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