Mechanistically, a decrease in intestinal-derived ceramides, as a result of lower ceramide synthesis-related genes by inhibition of FXR, likely mediates the resolution of the HFD-induced obesity and hepatic steatosis by Gly-MCA, although at this time it is uncertain whether ceramides affect insulin resistance. The gene discussed is NR1H4; the disease is obesity due to melanocortin 4 receptor deficiency.