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TLR ligands and butyrate increase Pyy expression through two distinct but inter-regulated pathways
Pierre Larraufie1, Joël Doré1,2, Nicolas Lapaque1
1MICALIS Institute, INRA, AgroParisTech, Université Paris-Saclay, France.
Cellular Microbiology
|July 13, 2016
Summary
Toll-like receptors (TLRs) are functionally expressed in human L-cells, modulating peptide YY (PYY) production. Bacterial fermentation product butyrate enhances TLR expression and sensing, impacting gut health and metabolic regulation.
Area of Science:
- Gastroenterology
- Immunology
- Endocrinology
Background:
- The intestinal epithelium acts as a barrier, sensing microbes via Toll-like receptors (TLRs).
- Enteroendocrine L-cells secrete PYY and GLP-1, crucial for metabolic regulation, but their TLR expression is unknown.
- TLRs influence gut permeability and defensin release, but their role in L-cells is uninvestigated.
Purpose of the Study:
- To investigate the expression and function of TLRs in human L-cells.
- To determine the impact of TLR stimulation on PYY and GLP-1 secretion.
- To explore the interaction between microbial metabolites like butyrate and TLR signaling in L-cells.
Main Methods:
- Utilized a human L-cell model and an NF-κB reporter system.
- Stimulated cells with specific TLR agonists.
- Assessed PYY and Proglucagon expression changes.
- Investigated the effects of butyrate on TLR expression and signaling.
Main Results:
- Demonstrated functional expression of TLRs in human L-cells.
- TLR stimulation increased peptide YY (PYY) expression via NF-κB pathway, but not Proglucagon.
- Butyrate enhanced TLR expression (including TLR4) and potentiated TLR-induced PYY expression.
- Butyrate's effect on PYY expression was additive to TLR stimulation.
Conclusions:
- TLRs play a significant role in modulating PYY expression within intestinal L-cells.
- Butyrate, a bacterial metabolite, enhances L-cell TLR expression and sensing capabilities.
- This highlights the interplay between gut microbiota, TLRs, and host metabolic regulation, relevant for obesity and type 2 diabetes.
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