Up-Regulation of the Uncoupling Protein Family by Chronic Treatment with a .BETA.3-Adrenergic Receptor Agonist in Obese Yellow KK Mice

Abstract

Chronic stimulation of the β3-adrenergic receptor in obese mice resulted in a reduced adiposity associated with the promotion of lipolysis and the increase of non-shivering thermogenesis. It is known that the mitochondrial uncoupling protein 1 (UCP 1) in brown adipose tissue (BAT) is an important key molecule for non-shivering thermogenesis. UCP2 and UCP3 were recently cloned, but the effect on the UCP family (UCP1, UCP2, and UCP3) of a β3-adrenergic receptor agonist is unclear. Therefore, in this study, the effect of a β3-adrenergic receptor agonist on UCP1, UCP2, and UCP3 was investigated in BAT, white adipose tissue (WAT) and the gastrocnemius muscle of C57BL control and obese yellow KK mice administered with a β3-adrenergic receptor agonist, CL316, 243 for two weeks subcutaneously. UCP1 mRNA was found abundantly in BAT, but detected only slightly in subcutaneous and perimetric WAT and gastrocnemius muscle in both C57BL and yellow KK mice. UCP2 mRNA and UCP3 mRNA were also found in all of tissues examined in both mice. Daily injections of CL316, 243 resulted in a reduction of body weight and white pad weight, and in increases in the mRNA levels of UCP1 in BAT, WAT, and gastrocnemius muscle, UCP2 in BAT and WAT, UCP3 in BAT and perimetric WAT in both groups. These results suggest that a β3-adrenergic receptor agonist up-regulates not only UCP1 mRNA in BAT, WAT, and gastrocnemius muscle, but also UCP2 and UCP3 mRNA in BAT and WAT, and the whole UCP family may contribute to increased thermogenesis and anti-obesity action following the administration of a β3-adrenergic receptor agonist.