Acta Veterinaria Brno

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In this study, the lipolytic effect of two newly synthesized potential β₃-adrenergic agonists A482 and B496 in active acid forms was tested using isolated sliced epididymal adipose tissue of Wistar rats, and compared with Isoprenaline and BRL37344. Furthermore, effects of an eight-week oral administration of the newly synthesized substances on serum cholesterol, triglycerides, glucose, adiponectin, resistin and weight gain were studied in C57Bl/6J mice that were fed high energy diet. The newly synthesized substance A482 (4-(2-{[2-hydroxy-3-(4-methyl-carbamoylphenoxy) propyl]amino}ethyl)phenoxy-acetic acid hydrochloride) was able to produce almost full lipolysis at a 1 × 10^-7 M concentration, and its effect on the rat epididymal adipose tissue was similar to the specific β₃-adrenergic agonist BRL37344. Ethyl ester of this substance significantly lowered plasma total cholesterol (p < 0.001), resistin (p < 0.01), weight gain (p < 0.01), improved total/HDL-cholesterol ratio (p < 0.01) and increased circulating adiponectin (p < 0.001) in C57Bl/6J mice that were fed high energy diet. The second tested substance B496 did not show all activities expected from β₃-adrenergic agonists. Our results suggest that the newly synthesised substance A482 may represent a potent β₃-adrenergic agonist.

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