Hyocholic acid and glycemic regulation: comments on ‘Hyocholic acid species improve glucose homeostasis through a distinct TGR5 and FXR signaling mechanism’

Wei Jia,Weiping Jia,Cynthia Rajani,Xiaojiao Zheng

doi:10.1093/jmcb/mjab027

Abstract

Hyocholic acid species (HCA, hyodeoxycholic acid, and their glycine and taurine conjugated forms) comprise 80% of the composition of pig bile (Haslewood, 1956). An interesting fact about pigs is that they do not get diabetes even though they eat almost anything and in abundant amounts, a diabetes-promoting diet. The first use of pig bile for treatment of 'xiao-ke', a condition known today as diabetes, was recorded ∼400 years ago by the Chinese medical practitioners in the Compendium of Materia Medica (Li, 1573‒1593). Recently, we found HCA species as novel biomarkers for metabolic diseases (Zheng et al., 2021b) and also identified the role of HCA species in the prevention of diabetes as well as their mechanism of action (Zheng et al., 2021a). Although bile acids (BAs) are mostly associated with their aid in food digestion, they have also been shown to act as signaling molecules by binding to two particular receptors, farnesoid X receptor (FXR) and the G-protein-coupled receptor, TGR5. Experiments were thus directed to the effect of HCA binding to these two BA receptors on glycemic regulation in both in vivo and in vitro models.

Highlights

The first in vivo experiment was done using pigs
Three groups of pigs were fed GW4064, an farnesoid X receptor (FXR) agonist that caused significant suppression of HCA species production, along with 30% increase in blood glucose levels and 69% decrease in blood glucagon-like peptide-1 (GLP-1) levels
At low bile acids (BAs) concentration (5 mM), there was no increase in GLP-1 secretion or production, while at higher concentration (25 mM), all of the HCA species and the TGR5 agonists, lithocholic acid (LCA) and deoxycholic acid (DCA), stimulated GLP-1 secretion within 1 h and after 24 h

Summary

Introduction

Three groups of pigs were fed GW4064, an FXR agonist that caused significant suppression of HCA species production, along with 30% increase in blood glucose levels and 69% decrease in blood glucagon-like peptide-1 (GLP-1) levels. When HCA species were administered, the blood glucose levels decreased and circulating GLP-1 increased, suggesting that glucose homeostasis and GLP-1 secretion were regulated by HCA species. Circulating GLP-1 levels were significantly increased in the HCA group.

Results

Conclusion