Some recent studies suggest that BSH activity alters gut microbiota and reduces obesity in mice through an FXR-mediated mechanism (Li et al., 2013; Liang et al., 2021), while unconjugated BAs affect TGR5-mediated adipose tissue development and weight loss (Svensson et al., 2013), and that there is a subtle interplay between FXR and TGR5 that warrants further investigations. This evidence concerns the gene GPBAR1 and obesity due to melanocortin 4 receptor deficiency.