Oleoyl-estrone lowers the body weight of both ob/ob and db/db mice

Homozygous obese db/db (BKS-Lepr(db) and ob/ob (B6-Lep(ob)) mice were treat ed for 14 days with a continuous infusion of a fat emulsion (controls) or l oaded with oleoyl-estrone at doses of 12.5 and 50 nmol/g x d using surgical ly inserted osmotic minipumps. Treatment with oleoyl-estrone resulted in a marked decrease in body weight in both strains, compared with the unchecked growth of controls. In db/db mice, plasma urea and insulin, as well as liv er lipid decreased with treatment. In ob/ob mice, the effect on insulin was more marked, in parallel with higher plasma lipids pointing to increased f at mobilisation. The results suggest that oleoyl-estrone effects on body fa t reserves and insulin resistance are not mediated by leptin, since ob/ob m ice lack this hormone and in the db/db it is present but cannot induce effe cts because of defective leptin receptors; in both cases oleoyl-estrone tre atment lowers body weight.