Anti-obesity effects of selective agonists to the beta 3-adrenergic receptor in dogs. I. The presence of canine beta 3-adrenergic receptor and in vivo lipomobilization by its agonists.
It is known that in rodents and humans the beta 3-adrenergic receptor (beta 3-AR) is present primarily in adipocytes and plays a significant role in the adrenergic stimulation of lipolysis. We examined the expression of beta 3-AR mRNA in the dog and the lipomobilizing effects of beta 3-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%) beta 3-AR cDNA. The beta 3-AR mRNA was present at high levels in subcutaneous and visceral adipose tissues, but undetectable in other organs. When a selective beta 3-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 beta 3-AR agonist, also showed a similar lipomobilizing effect, but with lower potency. beta 3-AR agonist infusion also increased the plasma insulin level. These results suggested that functional beta 3-AR is present in adipose tissues of the dog and that it is effective for in vivo lipomobilization.
Sasaki
N
N
Department of Biomedical Sciences, School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Uchida
E
E
Niiyama
M
M
Yoshida
T
T
Saito
M
M
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D008053:Lipid Mobilization / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009765:Obesity; D010642:Phenoxyacetates / Q000494:pharmacology*; D050198:Phenoxypropanolamines; D012333:RNA, Messenger / Q000096:biosynthesis; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D000316:Adrenergic alpha-Agonists; D001786:Blood Glucose; D004149:Dioxoles; D007328:Insulin; D010642:Phenoxyacetates; D050198:Phenoxypropanolamines; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; C071909:ICI D7114; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate