Treatment with BAR502 causes a 10% reduction of b.w., increases insulin sensitivity and circulating levels of HDL, while reduces steatosis, inflammatory and fibrosis scores and liver expression of SREPB1c, FAS, PPARγ, CD36 and CYP7A1 mRNA. BAR502 increases the expression of SHP and ABCG5 in the liver and SHP, FGF15 and GLP1 in intestine. BAR502 promotes the browning of epWAT and reduces liver fibrosis induced by CCl4. In models of non-obstructive cholestasis, BAR502 attenuates liver injury without causing itching. Co-treatment with BAR502 increases survival, attenuates serum alkaline phosphatase levels and robustly modulates the liver expression of canonical FXR target genes including OSTα, BSEP, SHP and MDR1, without inducing pruritus.