Lipolytic and hypolipidemic properties of newly synthesized aryloxypropanolamine derivatives.

摘要

In this study, the lipolytic effect of 2 newly synthesized potential beta ₃-adrenergic agonists, A482 and B496, in active acid forms was tested using isolated sliced epididymal adipose tissue of Wistar rats and compared with isoprenalineand BRL37344. Furthermore, the effects of an 8-week oral administration of the newly synthesized substances on serum cholesterol, triglycerides, glucose, adiponectin, resistin and weight gain were studied in C57B1/6J mice that were fed a high-energy diet. The newly synthesized substance, A482 (4-(2-{[2-hydroxy-3-(4-methyl-carbamoyl-phenoxy)propyl]amino}ethyl)phenoxy-acetic acid hydrochloride), was able to produce almost full lipolysis at a 1x10-7 M concentration, and its effect on the rat epididymal adipose tissue was similar to the specific beta ₃-adrenergic agonist BRL37344. The ethyl ester of this substance significantly lowered the plasma total cholesterol (p<0.001), resistin (p<0.01) and weight gain (p<0.01) but improved the total/HDL-cholesterol ratio (p<0.01) and increased the circulating adiponectin (p<0.001) in C57B1/6J mice that were fed a high-energy diet. The second tested substance, B496, did not show all activities expected from beta ₃-adrenergic agonists. The results suggested that the newly synthesized substance, A482, might represent a potent beta ₃-adrenergic agonist.