Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Modulation of Endocannabinoids by Caloric Restriction is Conserved in Mice but is not Required for the Protection from Acute Kidney Injury

K. Johanna R. Hoyer-Allo
,
Martin Richard Späth
,
Ruth Hanssen
,
Marc Johnsen
,
Susanne Brodesser
ORCID logo ,
Kathrin Kaufmann
,
Katharina Kiefer
,
Felix C. Koehler
,
Heike Göbel
,
Torsten Kubacki
,
Franziska Grundmann
,
Bernhard Schermer
,
Jens Brüning
,
Thomas Benzing
,
Volker Burst
,
Roman-Ulrich Müller
* ORCID logo
Version 1 : Received: 3 May 2021 / Approved: 5 May 2021 / Online: 5 May 2021 (13:59:13 CEST)

A peer-reviewed article of this Preprint also exists.

Hoyer-Allo, K.J.R.; Späth, M.R.; Hanssen, R.; Johnsen, M.; Brodesser, S.; Kaufmann, K.; Kiefer, K.; Koehler, F.C.; Göbel, H.; Kubacki, T.; Grundmann, F.; Schermer, B.; Brüning, J.; Benzing, T.; Burst, V.; Müller, R.-U. Modulation of Endocannabinoids by Caloric Restriction Is Conserved in Mice but Is Not Required for Protection from Acute Kidney Injury. Int. J. Mol. Sci. 2021, 22, 5485. Hoyer-Allo, K.J.R.; Späth, M.R.; Hanssen, R.; Johnsen, M.; Brodesser, S.; Kaufmann, K.; Kiefer, K.; Koehler, F.C.; Göbel, H.; Kubacki, T.; Grundmann, F.; Schermer, B.; Brüning, J.; Benzing, T.; Burst, V.; Müller, R.-U. Modulation of Endocannabinoids by Caloric Restriction Is Conserved in Mice but Is Not Required for Protection from Acute Kidney Injury. Int. J. Mol. Sci. 2021, 22, 5485.

Abstract

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

Keywords

acute kidney injury; ischemia-reperfusion injury; dietary restriction; nutrition; preconditioning; endocannabinoids; AEA

Subject

Medicine and Pharmacology, Immunology and Allergy

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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