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Microbiota-Generated Metabolites Promote Metabolic Benefits via Gut-Brain Neural Circuits

Abstract : Soluble dietary fibers promote metabolic benefits on body weight and glucose control, but underlying mechanisms are poorly understood. Recent evidence indicates that intestinal gluconeogenesis (IGN) has beneficial effects on glucose and energy homeostasis. Here, we show that the short-chain fatty acids (SCFAs) propionate and butyrate, which are generated by fermentation of soluble fiber by the gut microbiota, activate IGN via complementary mechanisms. Butyrate activates IGN gene expression through a cAMP-dependent mechanism, while propionate, itself a substrate of IGN, activates IGN gene expression via a gut-brain neural circuit involving the fatty acid receptor FFAR3. The metabolic benefits on body weight and glucose control induced by SCFAs or dietary fiber in normal mice are absent in mice deficient for IGN, despite similar modifications in gut microbiota composition. Thus, the regulation of IGN is necessary for the metabolic benefits associated with SCFAs and soluble fiber.
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https://www.hal.inserm.fr/inserm-03574751
Contributor : Marie-Ange Di Carlo Connect in order to contact the contributor
Submitted on : Tuesday, February 15, 2022 - 11:52:23 AM
Last modification on : Friday, August 5, 2022 - 12:31:37 PM
Long-term archiving on: : Monday, May 16, 2022 - 7:40:09 PM

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Filipe de Vadder, Petia Kovatcheva-Datchary, Daisy Goncalves, Jennifer Vinera, Carine Zitoun, et al.. Microbiota-Generated Metabolites Promote Metabolic Benefits via Gut-Brain Neural Circuits. Cell, Elsevier, 2014, 156 (1-2), pp.84-96. ⟨10.1016/j.cell.2013.12.016⟩. ⟨inserm-03574751⟩

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