Recently, it was shown that FXR deficiency in mice prevents genetic and diet-induced obesity, insulin resistance, and NAFLD (Prawitt et al., 2011; Gonzalez et al., 2016), while long-term administration of the synthetic FXR agonist GW4064 leads to lipid accumulation in liver in mice fed high-fat diet (Watanabe et al., 2011). Here, NR1H4 is linked to obesity due to melanocortin 4 receptor deficiency.