Abstract
Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors including PPARα, PPARγ, and PPARβ/δ, 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.
Highlights
Role of PPARα in Metabolism conditions of the Creative CommonsPPARα plays a major role in metabolic homeostasis regulating lipid metabolism
Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors including PPARα, PPARγ, and PPARβ/δ, 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
Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-activated receptors/transcriptional factors composed by three distinct isoforms called PPARα, PPARβ/δ (NR1C2), and PPARγ (NR1C3), each of which is encoded by independent genes in rodents and humans
Summary
PPARα plays a major role in metabolic homeostasis regulating lipid metabolism. During the fed-to-fasted transition, PPARα drives the production of enzymes responsible for fatty acid oxidation (FAO) and the synthesis of ketone bodies from fatty. Thereby, PPARα works as a hub that integrates multiple metabolic signals to orchestrate the switch from glucose to fatty acid utilization for energy production [10,11]. Studies on PPARα in other tissues including the heart, small intestine, skeletal muscle and brain have indicated that the role of PPARα in metabolic homeostasis is well conserved between different cell types [12,13,14,15]. Under fasting conditions or a high-fat diet, Pparα KO mice develop hypoglycemia and dyslipidemia characterized by excessive production of triacylglycerols [13,16,17]. The Pparα KO mouse model still shows unresolved aspects that are most likely attributable to the compensatory role of the other two PPAR isotypes, it allowed a deeper understanding of the role of PPARα in energy metabolism
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
