Anti-obesity effects of selective agonists to the beta 3-adrenergic receptor in dogs. II. Recruitment of thermogenic brown adipocytes and reduction of adiposity after chronic treatment with a beta 3-adrenergic agonist.
The aim of this study was to evaluate the effectiveness of beta 3-adrenergic agonists for the treatment and prevention of obesity in the dog. When a selective beta 3-adrenergic agonist, CL316,243 (0.1 mg/kg), was given orally to adult beagles every day for 5-7 weeks, body weight and girth were decreased compared with control placebo-treated dogs. Gross anatomical examinations revealed no noticeable abnormalities in CL316,243-treated dogs, except an apparent decrease in abdominal fat. Immunohistochemical examination of perirenal adipose tissue showed a remarkable increase in brown adipocytes expressing a thermogenic protein, uncoupling protein (UCP). The increased expression of UCP and its mRNA in CL316,243-treated dogs was also confirmed by Western blot and reverse transcription polymerase chain reaction analyses. It was concluded that treatment with a beta 3-adrenergic agonist stimulates UCP expression, which may lead to an increase in energy expenditure, and thereby is useful for the treatment and prevention of obesity in the dog.
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
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000502:physiology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001824:Body Constitution; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000096:biosynthesis; D004149:Dioxoles / Q000494:pharmacology*; D004283:Dog Diseases; D004285:Dogs; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007473:Ion Channels; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D024101:Mitochondrial Proteins; D009765:Obesity / Q000517:prevention & control / Q000662:veterinary*; D012333:RNA, Messenger / Q000096:biosynthesis; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3; D014158:Transcription, Genetic / Q000187:drug effects; D000071256:Uncoupling Protein 1
D000318:Adrenergic beta-Agonists; D002352:Carrier Proteins; D004149:Dioxoles; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D000071256:Uncoupling Protein 1; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate