Endocannabinoid-related molecules predict the metabolic efficacy of GLP-1 receptor agonism in humans with obesity
J Endocrinol Invest. 2023-11-04; :
DOI: 10.1007/s40618-023-02228-8
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Matias I(1), Lehmann EW(2), Zizzari P(1), Byberg S(2), Cota D(1), Torekov SS(3), Quarta C(4)(5).
Author information:
(1)University of Bordeaux, INSERM, Neurocentre Magendie, U1215, 33000, Bordeaux, France.
(2)Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
(3)Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark. .
(4)University of Bordeaux, INSERM, Neurocentre Magendie, U1215, 33000, Bordeaux, France. .
(5)INSERM U1215, Neurocentre Magendie, 146 Rue Léo Saignat, 33077, Bordeaux Cedex, France. .
OBJECTIVE: N-acylethanolamines (NAEs) include endocannabinoid (EC) and C-related molecules that impact the anti-obesity and anti-diabetic efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RA) in animal studies. However, the clinical relevance of these findings remains to be determined. Here, we tested whether GLP-1RA treatment affects circulating NAE levels and whether NAEs may predict the efficacy of GLP-1RA treatment in humans with obesity undergoing weight loss maintenance.
MATERIALS AND METHODS: We profiled plasma levels of NAEs in participants with obesity undergoing weight loss maintenance with (n = 23)/or without (n = 20) treatment with the GLP-1RA liraglutide. NAE levels were measured at three different time points: before the start of the study, at the end of the
diet-induced weight loss, and after 52-weeks treatment. Linear regression analyses were used to investigate whether pharmacological responses could be predicted by NAEs levels.
RESULTS: Liraglutide treatment reduced plasma concentrations of the NAE and oleoyl-ethanolamide (OEA), without altering arachidonoyl-ethanolamide (AEA) levels and palmitoyl-ethanolamide (PEA) levels. High pre-treatment levels of OEA were predictive of superior compound-mediated effects on fasting insulin and triglyceride levels. High pre-treatment PEA and AEA levels were also predictive of superior Liraglutide-mediated effects on triglyceride levels.
CONCLUSIONS: Our data suggests that specific NAEs such as OEA and AEA are promising biomarkers of GLP-1RA metabolic efficacy in humans with obesity during weight loss maintenance. Plasma profiling of EC-related molecules may be a promising strategy to tailor GLP-1R-based therapies to individual needs in obesity and diabetes management.
© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).