Serotonin receptor 4 agonism prevents high fat diet induced reduction in GLP-1 in mice

Nov 5, 2023European journal of pharmacology

Activating serotonin receptor 4 stops a high-fat diet from lowering GLP-1 levels in mice

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Two weeks of high fat diet feeding reduced RNA expression of gut hormones, including proglucagon and Tryptophan hydroxylase1, specifically in the colon.

High fat diet led to decreased plasma GLP-1 levels.
Reduced levels of the gut metabolites propionate and butyrate were observed following high fat diet.
Sodium propionate supplementation did not reverse the high fat diet-induced reduction in GLP-1.
Chemical activation of serotonin receptor 4 increased GLP-1 levels and colonic Gcg RNA expression.
Improvement in glucose tolerance was noted in high fat diet-fed mice following serotonin receptor 4 stimulation.

AI simplified

Hormone-producing enteroendocrine cells (EECs) are present throughout the gastrointestinal tract and respond to various nutrient and gut microbiota produced metabolites stimuli. Two important EEC subtypes, Glucagon like peptide-1 (GLP-1) producing L-cells and serotonin (5-HT) producing enterochromaffin (EC) cells interact via paracrine signaling and exhibit bidirectional regulation of expression and secretion of produced hormones. Accordingly, in vitro studies suggest potential to modulate 5-HT secretion by GLP-1 receptor agonism, and L-cell differentiation via serotonin receptor 4 agonism. However, the importance of this cellular signaling on host metabolism is poorly understood. In this study, we found that two weeks of high fat diet (HFD) feeding reduced RNA expression of gut hormones, including proglucagon (Gcg) gene encoding GLP-1 and Tryptophan hydroxylase1 (Tph1) gene encoding rate limiting enzyme in 5-HT synthesis, specifically in the colon and reduced plasma GLP-1 levels. Levels of propionate and butyrate were also reduced following HFD. However, supplementation of sodium propionate did not improve HFD induced reduction in GLP-1. In contrast, chemical induction of serotonin receptor 4 promoted GLP-1 levels, colonic Gcg RNA expression accompanied by improvement in glucose tolerance in HFD-fed mouse. Thus, this study suggests a novel mechanism to improve glucose tolerance via serotonin receptor 4 stimulation in the HFD induced obese mouse model.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Serotonin receptor 4 agonism prevents high fat diet induced reduction in GLP-1 in mice

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief