Effect of CL316, 243, a Highly Specific β₃-Adrenoceptor Agonist, on Lipolysis of Epididymal, Mesenteric and Subcutaneous Adipocytes in Rats

抄録

To clarify whether β₃-adrenoceptor agonist is more lipolytic in the visceral adipocytes than in the subcutaneous adipocytes, the lipolysis induced by CL316, 243, a highly specific β₃-adrenoceptor agonist (relative selectivities of 0, 1 and 100, 000 for β₁-, β₂- and β₃-receptors, respectively) was investigated in adipose tissue from rats. White adipocytes were prepared from the subcutaneous, mesenteric, and epididymal white adipose tissues of male Wistar rats (weighing about 150g). Our findings showed that lipolysis of white adipocytes was stimulated both by the non-specific β- adrenoceptor agonist, isoproterenol, and by the β₃-specific adrenoceptor agonist, CL316, 243, but the lipolytic sensitivity to CL316, 243 was about 10 times greater than that to isoproterenol in these three adipose tissues. Both isoproterenol and CL316, 243 induced more noticeable lipolysis in the epididymal and mesenteric than in the subcutaneous adipose cells in terms of the pD₂ value [-log mol 1^-1 for EC₅₀ (the concentration of an agonist giving half of its own maximum stimulation)]. These findings show that CL316, 243 is more lipolytic in the visceral adipose cells than in the subcutaneous adipose cells, although epididymal adipose cells showed a high lipolytic response close to those observed in visceral adipose cells. CL316, 243 may therefore be especially useful for the treatment of visceral fat type obesity related to various diseases.