Peroxisome proliferator-activated receptors (PPARs) are fatty acid-activated transcription factors of nuclear hormone receptor superfamily that regulate energy metabolism. Currently, three PPAR subtypes have been identified: PPARα, PPARγ, and PPARβ/δ. PPARα and PPARδ are highly expressed in oxidative tissues and regulate genes involved in substrate delivery and oxidative phosphorylation and regulation of energy homeostasis. In contrast, PPARγ is more important in lipogenesis and lipid synthesis, with highest expression levels in white adipose tissue. In addition to tissues regulating whole body energy homeostasis, PPARs are expressed in immune cells and have an emerging critical role in immune cell differentiation and fate commitment.
In their review, A. Christofides and colleagues (Division of Hematology-Oncology, Department of Medicine, and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts) discuss the actions of PPARs in the function of the innate and the adaptive immune system and their implications in immune-mediated inflammatory. Members of the PPAR family of nuclear hormone receptors are well- established regulators of lipid metabolism, mitochondrial biogenesis and energy homeostasis. Their activation has central implications in the function of oxidative tissues and organs such as cardiomyocytes, liver and muscle.
For many years, PPARs have been attractive therapeutic targets for the treatment of metabolic disorders. The role of various members of this nuclear receptor family is currently emerging in the differentiation and function of immune cells as they guide metabolism- mediated immune cell fate commitment.