The Endocannabinoid System and PPARs: Focus on Their Signalling Crosstalk, Action and Transcriptional Regulation

Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors including PPAR alpha, PPAR gamma, and PPAR beta/delta, acting as transcription factors to regulate the expression of a plethora of target genes involved in metabolism, immune reaction, cell differentiation, and a variety of other cellular changes and adaptive responses. PPARs are activated by a large number of both endogenous and exogenous lipid molecules, including phyto- and endo-cannabinoids, as well as endocannabinoid-like compounds. In this view, they can be considered an extension of the endocannabinoid system. Besides being directly activated by cannabinoids, PPARs are also indirectly modulated by receptors and enzymes regulating the activity and metabolism of endocannabinoids, and, vice versa, the expression of these receptors and enzymes may be regulated by PPARs. In this review, we provide an overview of the crosstalk between cannabinoids and PPARs, and the importance of their reciprocal regulation and modulation by common ligands, including those belonging to the extended endocannabinoid system (or endocannabinoidome) in the control of major physiological and pathophysiological functions.

Automated summary

PPARs are a family of nuclear receptors that regulate the expression of target genes involved in metabolism, immune reaction, cell differentiation, and other cellular changes. They are activated by various lipid molecules, including cannabinoids, and interact with the endocannabinoid system to modulate physiological and pathophysiological functions.