Endocannabinoid-related molecules predict the metabolic efficacy of GLP-1 receptor agonism in humans with obesity

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Objective: N-acylethanolamines (NAEs) include endocannabinoid (EC) and EC-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.

TidsskriftJournal of Endocrinological Investigation
Antal sider8
StatusE-pub ahead of print - 2024

Bibliografisk note

Funding Information:
We acknowledge INSERM (DC and CQ), Nouvelle Aquitaine Region (DC), University of Bordeaux’s IdEx ‘Investments for the Future’ program/GPR BRAIN_2030 (DC), Agence Nationale Recherche (Labex BRAIN ANR-10-LABX-43, ANR-18-CE14-0029, ANR-21-CE14-0018, ANR-22-CE14-0016 to DC; ANR-20-CE14-0046 to CQ), French Societies of Endocrinology, Nutrition, and Diabetes (SFE, SFN, and SFD), Fyssen Foundation, and Institut Benjamin Delessert (CQ), Excellence grant (NNF16OC0019968, to ST) and Novo Nordisk Foundation.

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).

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