Chronic effects of AJ-9677 on energy expenditure and energy source utilization in rats.
The effects of AJ-9677 on metabolic parameters were examined in rats that had or had not been chronically treated with this beta3-adrenoceptor agonist. A challenge administration of AJ-9677 increased both the temperature of brown adipose tissue and energy expenditure in both groups of rats. However, whereas the former effect was subject to desensitization, the latter effect was augmented by prior chronic administration of AJ-9677. Whereas a challenge administration of AJ-9677 induced a decrease in the respiratory quotient that persisted for at least 15 h in rats pretreated with vehicle, the initial decrease in this parameter lasted for only 4 h in rats pretreated with AJ-9677. These results suggest that, in rats subjected to chronic treatment with AJ-9677, a challenge administration of this drug increased energy expenditure by stimulation not only of fat oxidation but also of glucose oxidation.
Sugimoto
Tadanori
T
Biostatistics, Drug Development Division, Dainippon Pharmaceutical Co. Ltd., Suita, Osaka 564-0053, Japan. tadanori-sugimoto@dainippon-pharm.co.jp
Ogawa
Wataru
W
Kasuga
Masato
M
Yokoyama
Yuichi
Y
D000085:Acetates; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000502:physiology; D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D001831:Body Temperature / Q000187:drug effects; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics; D003243:Consciousness; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007473:Ion Channels; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D024101:Mitochondrial Proteins; D010101:Oxygen Consumption / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics; D013997:Time Factors; D000071256:Uncoupling Protein 1
C418363:((3-((2R)-(((2R)-3-chlorophenyl)-2-hydroxyethyl)amino)propyl)-1H-indol-7-yloxy)acetic acid; C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D000085:Acetates; D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D002352:Carrier Proteins; D005230:Fatty Acids, Nonesterified; D007211:Indoles; D007328:Insulin; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011412:Propanolamines; D012333:RNA, Messenger; D022702:Receptors, Adrenergic, beta-3; D000071256:Uncoupling Protein 1; D001262:Atenolol; D000242:Cyclic AMP; D005947:Glucose