NR0B2 and obesity due to melanocortin 4 receptor deficiency: While intestinal FXR inhibition has demonstrated efficacy against obesity, diabetes, and MASLD through mechanisms such as suppressing hepatic gluconeogenesis via SHP-independent enterohepatic signaling [87,88] and reducing hepatic lipid accumulation through suppression of SHP and FGF15/FGF19 expression, contrasting evidence highlights the metabolic benefits of hepatic FXR activation.