Modulation of Endocannabinoids by Caloric Restriction Is Conserved in Mice but Is Not Required for Protection from Acute Kidney Injury

Acute kidney injury (AKI) is a frequent and critical complication in the clinical setting. In rodents, AKI can be effectively prevented through caloric restriction (CR), which has also been shown to increase lifespan many species. Caenorhabditis elegans (C. elegans), longevity studies revealed that marked CR-induced reduction of endocannabinoids may key mechanism. Thus, we hypothesized regulation endocannabinoids, particularly arachidonoyl ethanolamide (AEA), might play role CR-mediated protection from renal ischemia-reperfusion (IRI) mammals including humans. male C57Bl6J mice, CR significantly reduced IRI led significant decrease AEA. Supplementation AEA near-normal serum concentrations by repetitive intraperitoneal administration however, did not abrogate protective effect CR. We analyzed samples taken before after patients three different pilot trials dietary interventions. contrast mice C. elegans, detected an conclude endocannabinoid levels are modulated CR, but does depend on this effect. Moreover, our results indicate modulation humans differ fundamentally effects animal models.