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- doi: 10.1038/s42255-021-00398-4
- issn: 2522-5812
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Domestic animals--Feeding and feeds Feeding of animals Livestock--Feeding and feeds Feeding Feeding, Animal Animals--Feeding and feeds Nervous system, Central Cerebrum MindCiter ce document
A. Perino et al., « Central anorexigenic actions of bile acids are mediated by TGR5. », Serveur académique Lausannois, ID : 10.1038/s42255-021-00398-4
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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 brain 1 , 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 BAs 2 and an established regulator of peripheral metabolism 3-8 . 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.