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Open AccessArticle

Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists

1
Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life sciences and BIOtechnology (WELBIO), UCLouvain, Université Catholique de Louvain, Av. E. Mounier, 73 B1.73.11, 1200 Brussels, Belgium
2
Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, 80078 Pozzuoli, Italy
3
Quebec Heart and Lung Institute Research Centre, Université Laval, Quebec City, QC G1V 0A6, Canada
4
Centre NUTRISS, Institute of Nutrition and Functional Foods, Université Laval, Quebec City, QC G1V 0A6, Canada
5
Pôle EDIN, Institut de Recherches Expérimentales et Cliniques, UCLouvain, Université catholique de Louvain, 1200 Brussels, Belgium
6
Division of Endocrinology and Nutrition, Cliniques Universitaires St-Luc, 1200 Brussels, Belgium
7
Laboratory of Microbiology, Wageningen University, 6708WE Wageningen, The Netherlands
8
Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
*
Authors to whom correspondence should be addressed.
These authors contributed equally to the manuscript.
Cells 2021, 10(1), 185; https://doi.org/10.3390/cells10010185
Received: 17 December 2020 / Revised: 14 January 2021 / Accepted: 14 January 2021 / Published: 19 January 2021
Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome. View Full-Text
Keywords: endocannabinoids; endocannabinoidome; Akkermansia muciniphila; human; metabolic syndrome; obesity; mono-palmitoyl-glycerol; peroxisome proliferator-activated receptor alpha (PPARα) endocannabinoids; endocannabinoidome; Akkermansia muciniphila; human; metabolic syndrome; obesity; mono-palmitoyl-glycerol; peroxisome proliferator-activated receptor alpha (PPARα)
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MDPI and ACS Style

Depommier, C.; Vitale, R.M.; Iannotti, F.A.; Silvestri, C.; Flamand, N.; Druart, C.; Everard, A.; Pelicaen, R.; Maiter, D.; Thissen, J.-P.; Loumaye, A.; Hermans, M.P.; Delzenne, N.M.; de Vos, W.M.; Di Marzo, V.; Cani, P.D. Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists. Cells 2021, 10, 185. https://doi.org/10.3390/cells10010185

AMA Style

Depommier C, Vitale RM, Iannotti FA, Silvestri C, Flamand N, Druart C, Everard A, Pelicaen R, Maiter D, Thissen J-P, Loumaye A, Hermans MP, Delzenne NM, de Vos WM, Di Marzo V, Cani PD. Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists. Cells. 2021; 10(1):185. https://doi.org/10.3390/cells10010185

Chicago/Turabian Style

Depommier, Clara; Vitale, Rosa M.; Iannotti, Fabio A.; Silvestri, Cristoforo; Flamand, Nicolas; Druart, Céline; Everard, Amandine; Pelicaen, Rudy; Maiter, Dominique; Thissen, Jean-Paul; Loumaye, Audrey; Hermans, Michel P.; Delzenne, Nathalie M.; de Vos, Willem M.; Di Marzo, Vincenzo; Cani, Patrice D. 2021. "Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists" Cells 10, no. 1: 185. https://doi.org/10.3390/cells10010185

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