FXR knockout/deficient mice exhibit decreased adipose tissue, lower leptin concentrations, elevated plasma free fatty acids, resistance to rosiglitazone-induced obesity, and their embryonic fibroblasts are also resistant to rosiglitazone-induced triglyceride accumulation and differentiation due to increased lipolysis and decreased lipogenesis (113, 117, 118); despite these apparent positive metabolic effects, FXR deficient animals (both mice and rabbits) also exhibit impaired glucose tolerance and insulin resistance, which are corrected with FXR agonist supplementation (113, 119). Here, NR1H4 is linked to Impaired glucose tolerance.