# Liraglutide upregulates the Cftr gene and regulates the mucus transcriptome profile in Brunner's glands in mice

## TL;DR

Liraglutide, a drug used for metabolic syndrome, boosts mucus production in mouse Brunner's glands by activating a specific receptor, which may help improve gut health.

## Contribution

This study reveals a new mechanism by which liraglutide activates genes in Brunner's glands to enhance mucus production and gut barrier function.

## Key findings

- Liraglutide upregulates the Cftr gene in Brunner's glands via GLP-1R activation.
- Liraglutide increases expression of Muc5b, Il33, Ren1, and Vldlr genes in Brunner's glands.
- The drug induces a genetic profile linked to mucus secretion and hydration in these glands.

## Abstract

The metabolic syndrome encompasses a state of inflammation and metabolic dysfunction, possibly mediated via a disturbed intestinal barrier. Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), such as liraglutide, have shown promising anti‐inflammatory effects beyond glucose lowering and weight loss, but the underlying mechanism remains to be elucidated. We hypothesised that GLP‐1RAs improve the intestinal barrier function and overall inflammatory status by direct gene activation in mucus‐secreting Brunner's glands in the mouse duodenum, known for their high density of glucagon‐like peptide‐1 receptors (GLP‐1Rs).

Using bulk RNA sequencing, in situ hybridisation, and immunohistochemistry, we analysed the change in the genetic phenotype of mouse Brunner's gland cells following GLP‐1R activation by liraglutide.

We show that liraglutide induces a novel and robust upregulation of the gene for the Cystic fibrosis transmembrane conductance regulator, Cftr, in Brunner's glands as a part of an overall genetic phenotype involved in ion channel activity, mucus secretion, and hydration via GLP‐1R activation. Additionally, we found a robust upregulation of the genes Muc5b, Il33, Ren1, and Vldlr in Brunner's glands.

Collectively, our results imply an enhanced mucus response from Brunner's glands following GLP‐1R activation, which might play a role in the effect of GLP‐1.

RNA sequencing, in situ hybridisation, and immunohistochemistry show that the glucagon‐like peptide‐1 receptor agonist liraglutide upregulates Cftr, Muc5b, Il33, Ren1, and Vldlr in Brunner's glands of mice.