PERINO, Alessia; VELAZQUEZ-VILLEGAS, Laura A.; BRESCIANI, Nadia; SUN, Yu; HUANG, Qingyao; FENELON, Valerie S.; CASTELLANOS-JANKIEWICZ, Ashley; ZIZZARI, Philippe; BRUSCHETTA, Giuseppe; JIN, Sungho; BALEISYTE, Aiste; GIOIELLO, Antimo; PELLICCIARI, Roberto; IVANISEVIC, Julijana; SCHNEIDER, Bernard L.; DIANO, Sabrina; COTA, Daniela; SCHOONJANS, Kristina

doi:10.1038/s42255-021-00398-4

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Nature Metabolism. 2021-05-01, vol. 3, n° 5, p. 595-603

Résumé en anglais

Bile acids (BAs) are signalling molecules that mediate various cellular responses in both physiological and pathological processes. Several studies report that BAs can be detected in the brain1, yet their physiological role in the central nervous system is still largely unknown. Here we show that postprandial BAs can reach the brain and activate a negative-feedback loop controlling satiety in response to physiological feeding via TGR5, a G-protein-coupled receptor activated by multiple conjugated and unconjugated BAs2 and an established regulator of peripheral metabolism3,4,5,6,7,8. Notably, peripheral or central administration of a BA mix or a TGR5-specific BA mimetic (INT-777) exerted an anorexigenic effect in wild-type mice, while whole-body, neuron-specific or agouti-related peptide neuronal TGR5 deletion caused a significant increase in food intake. Accordingly, orexigenic peptide expression and secretion were reduced after short-term TGR5 activation. In vitro studies demonstrated that activation of the Rho–ROCK–actin-remodelling pathway decreases orexigenic agouti-related peptide/neuropeptide Y (AgRP/NPY) release in a TGR5-dependent manner. Taken together, these data identify a signalling cascade by which BAs exert acute effects at the transition between fasting and feeding and prime the switch towards satiety, unveiling a previously unrecognized role of physiological feedback mediated by BAs in the central nervous system.< Réduire

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https://oskar-bordeaux.fr/handle/20.500.12278/128793

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http://dx.doi.org/10.1038/s42255-021-00398-4

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Développment d'une infrastructure française distribuée coordonnée
La signalisation des acides biliaires dans le cerveau et son rôle dans le contrôle métabolique
Innovations instrumentales et procédurales en psychopathologie expérimentale chez le rongeur - ANR-10-EQPX-0008

Unités de recherche

Neurocentre Magendie - U1215

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Central anorexigenic actions of bile acids are mediated by TGR5

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Résumé en anglais

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