NR1H4 and Insulin resistance: However, providing the synthetic FXR agonist GW4064—shown previously to be sufficient to decrease bile acid levels and energy expenditure thereby accentuating diet-induced weight gain and insulin resistance in mice (Watanabe et al., 2011)—was sufficient to decrease bile acids in eNOS-TG mice; however, the GW4064-supplemented eNOS-TG mice maintained their lean phenotype on HFD, and the drug did not affect glucose tolerance or insulin sensitivity.