Peroxisome Proliferator-Activated Receptors: The Nutritionally Controlled Molecular Networks that Integrate Inflammation, Immunity and Metabolism

PPARs are receptors for a highly diverse set of natural lipid molecules of nutritional or endogenous origin. While PPARs are involved in the regulation of metabolic, immune and inflammatory processes, no studies are available that integrate the metabolic and immunomodulatory properties of these receptors. Due to the therapeutic significance of selective agonists, the scientific understanding of PPARs biology derives primarily from experiments that utilized synthetic ligands. However, PPARs have existed in nature for millions of years prior to the development of synthetic ligands. This observation further supports the importance of endogenous/nutritional ligands as regulators of PPAR function. Therefore, the predominantly drug-based investigative approach may not reflect the actual physiological function of PPARs. The goal of this review article is to provide an integrative vision on the role of PPAR α, β/δ and γ, in the interface between metabolic and immunoinflammatory diseases. We will also discuss the differences and similarities between the effects of synthetic and natural PPAR agonists, and examine the actions of the three isoforms both separately and as a part of interconnected nuclear receptor networks. Finally, we will discuss the possible role of adipose tissue as an organ of innate immunity and the link between visceral adipose tissue accumulation and chronic, low-grade inflammatory responses. The better understanding of adipose tissue as an immunoendocrine organ may facilitate the development of novel PPAR-based interventions against metabolic and immune disorders.