NR1H4 and Insulin resistance: 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).