Endocannabinoid-related molecules predict the metabolic efficacy of GLP-1 receptor agonism in humans with obesity
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Endocannabinoid-related molecules predict the metabolic efficacy of GLP-1 receptor agonism in humans with obesity. / Matias, I.; Lehmann, E. W.; Zizzari, P.; Byberg, S.; Cota, D.; Torekov, S. S.; Quarta, C.
I: Journal of Endocrinological Investigation, Bind 43, 2024, s. 1289–1294.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Endocannabinoid-related molecules predict the metabolic efficacy of GLP-1 receptor agonism in humans with obesity
AU - Matias, I.
AU - Lehmann, E. W.
AU - Zizzari, P.
AU - Byberg, S.
AU - Cota, D.
AU - Torekov, S. S.
AU - Quarta, C.
N1 - Publisher Copyright: © 2023, The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Endocannabinoid-related molecules
KW - Endocannabinoids
KW - GLP-1R agonist
KW - Obesity
U2 - 10.1007/s40618-023-02228-8
DO - 10.1007/s40618-023-02228-8
M3 - Journal article
C2 - 37924474
AN - SCOPUS:85175692425
VL - 43
SP - 1289
EP - 1294
JO - Journal of Endocrinological Investigation
JF - Journal of Endocrinological Investigation
SN - 0391-4097
ER -
ID: 373470933