Glycine-β-muricholic Acid

Glycine-β-muricholic acid (GβMCA) is an intestine-selective antagonist of the farnesoid X receptor (FXR) and the glycine-conjugated form of the murine-specific primary bile acid β-muricholic acid .[1] [2]  It inhibits expression of the FXR target genes Shp and Fgf15 induced by the FXR ligands chenodeoxycholic acid and GW 4064 in Caco-2 cells when used at a concentration of 100 μM. GβMCA is resistant to hydrolysis by fecal bile salt hydrolase (BSH) isolated from gut microbiota, indicating gut stability. Dietary administration of GβMCA (10 mg/kg) decreases Shp and Fgf15 mRNA expression in ileum, but not liver, and reduces ceramide levels and expression of the ceramide synthesis-related genes Sptlc2, Sptlc3, Cers2, Cers4, Degs1, Degs2, Smpd3, and Smpd4 in ileum of mice with high-fat diet-induced obesity and db/db mice. It also prevents weight gain, reduces blood glucose levels, and increases insulin sensitivity as well as prevents development of cholestasis and necrotic lesions in liver of mice with high-fat diet-induced obesity.

Reference:
[1]. Jiang, C., Xie, C., Lv, Y., et al. Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction. Nat. Commun. 6, 10166 (2015).
[2]. Wahlström, A., Sayin, S.I., Marschall, H.-I., et al. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab. 24(1), 41-50 (2016).