title: TLR ligands and butyrate increase Pyy expression through two distinct but inter-regulated pathways.
abstract: The intestinal epithelium is an active barrier separating the host from its microbiota. It senses microbial compounds through expression of a wide range of receptors including the Toll-like receptors (TLRs). TLRs have been shown to regulate epithelium permeability or secretion of defensin by Paneth cells. However, the expression and function of TLRs in enteroendocrine L-cells, a specific subtype of intestinal cells secreting PYY and GLP-1, have not yet been assessed. PYY and GLP-1 are implicated in regulation of gut motility, food intake and insulin secretion, and are of great interest regarding obesity and type 2 diabetes. Using a cellular model of human L-cells and a reporter system for NF-κB activation pathway, we reported functional expression of TLRs in these cells. Stimulation with specific TLR-agonists increased expression of Pyy but not Proglucagon in an NF-κB-dependent manner. Moreover, the effect of TLR stimulation was additive to butyrate, a product of bacterial fermentation, on Pyy expression. Additionally, butyrate also increased Tlr expression, including Tlr4, and the NF-κB response to TLR stimulation. Altogether, our results demonstrated a role of TLRs in the modulation of Pyy expression and the importance of butyrate, a product of bacterial fermentation in regulation of microbial TLR-dependent sensing.
authors.affiliation: MICALIS Institute, INRA, AgroParisTech, Université Paris-Saclay, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Larraufie
authors.affiliation: MICALIS Institute, INRA, AgroParisTech, Université Paris-Saclay, France.|MGP MetaGenoPolis, INRA, Université Paris-Saclay, Jouy en Josas, France.
authors.forename: Joël
authors.initials: J
authors.lastname: Doré
authors.affiliation: MICALIS Institute, INRA, AgroParisTech, Université Paris-Saclay, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lapaque
authors.affiliation: MICALIS Institute, INRA, AgroParisTech, Université Paris-Saclay, France.|MGP MetaGenoPolis, INRA, Université Paris-Saclay, Jouy en Josas, France.
authors.forename: Hervé M
authors.initials: HM
authors.lastname: Blottière
mesh_terms: D002087:Butyrates / Q000378:metabolism*; D002460:Cell Line; D019858:Enteroendocrine Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000096:biosynthesis; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D019894:Peptide YY / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000819:agonists*
chemical_list: D002087:Butyrates; D016328:NF-kappa B; D051193:Toll-Like Receptors; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1