SHU9119 treatment potently increases metabolic efficiency. SHU9119 markedly increases mRNA levels of genes promoting lipogenesis and TAG storage in adipocytes, including stearoyl-CoA desaturase-1, lipoprotein lipase, acetyl-CoA carboxylase α, and fatty acid synthase. The blockade of CNS-Mcr via chronic intracerebroventricular infusion of SHU9119 (24 nmol/d for 7 days) increases food intake in ad libitum-fed rats compared with control. Weight gain of SHU9119 treated rats is significantly higher than control. SHU9119 increases food intake (+30%) and body fat (+50%) and decreases EE by a reduction in fat oxidation (?42%). SHU9119 impairs the uptake of VLDL-TG by BAT. SHU9119 reduces uncoupling protein-1 levels in BAT (?60%) and induces large intracellular lipid droplets, indicative of severely disturbed BAT activity [2][3].