Mice fed control or high-fat diet treated with fexaramine, an intestinal-specific FXR agonist, demonstrated increased energy expenditure, reduced body weight and body fat mass, decreased systemic inflammation and glucose production, and increased brown adipose tissue mass when compared with vehicle-treated mice on the high-fat diet.99 Because of the complex responses of tissue-restricted FXR activation, identifying tissue-specific or cell-specific modulators of FXR is required to develop safe and effective therapies for NAFL and NASH patients. Here, NR1H4 is linked to metabolic dysfunction-associated steatohepatitis.