Anti-Obesity Effects of Selective Agonists to the β3-Adrenergic Receptor in Dogs. I. The Presence of Canine β3-Adrenergic Receptor and in vivo Lipomobilization by Its Agonists

Abstract

It is known that in rodents and humans the β3-adrenergic receptor (β3-AR) is present primarily in adipocytes and plays a significant role in the adrenergic stimulation of lipolysis. We examined the expression of β3-AR mRNA in the dog and the lipomobilizing effects of β3-AR-selective agonists in vivo Reverse transcription polymerase chain reaction of RNA extracted from dog adipose tissue produced a cDNA fragment, the nucleotide sequence of which was highly homologous to the corresponding regions of human (86.4%) and mouse (79.5%) β3-AR cDNA. The β3-AR mRNA was present at high levels in subcutaneous and visceral adipose tissues, but undetectable in other organs. When a selective β3-AR agonist, CL316,243, was infused intravenously into beagle dogs, the plasma level of free fatty acid increased in 30 min and persisted at higher levels for several hours. ICI D7114, another β3-AR agonist, also showed a similar lipomobilizing effect, but with lower potency. β3-AR agonist infusion also increased the plasma insulin level. These results suggested that functional β3-AR is present in adipose tissues of the dog and that it is effective for in vivo lipomobilization.