beta 3-Adrenergic-mediated suppression of leptin gene expression in rats.
To investigate the role of beta 3-adrenergic receptors in the suppression of leptin gene expression, we fasted F-344 rats to decrease leptin mRNA levels, refed the rats to stimulate leptin mRNA production, and examined the ability of the beta 3-adrenergic agonist CGP-12177 to prevent the rise in leptin mRNA levels. In the initial 2 h after CGP-12177 (0.75 mg/kg), there were significant reductions in both food consumption and leptin mRNA levels in epididymal, perirenal, and interscapular white adipose tissue. We were unable to detect leptin mRNA in interscapular brown adipose tissue (IBAT), whereas there was a significant increase in uncoupling protein mRNA levels in IBAT after CGP-12177. The suppression of leptin mRNA and food intake by CGP-12177 was confirmed in a second experiment using another rat strain, the F-344 x BN. Furthermore, refeeding after a period of fasting increased leptin mRNA, which was prevented by CGP-12177. These data indicate a role for beta 3-adrenergic-mediated regulation of leptin gene expression in nonmutant rodents and are consistent with other reports suggesting that beta 3-adrenergic agonists suppress food intake.
Li
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Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville 32608-1197, USA.
Matheny
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M
Scarpace
P J
PJ
D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000096:biosynthesis; D003433:Crosses, Genetic; D007473:Ion Channels; D020738:Leptin; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D024101:Mitochondrial Proteins; D009765:Obesity; D011412:Propanolamines / Q000494:pharmacology*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3; D013489:Suppression, Genetic / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects*; D000071256:Uncoupling Protein 1
D000318:Adrenergic beta-Agonists; D002352:Carrier Proteins; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011412:Propanolamines; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D000071256:Uncoupling Protein 1; C033394:CGP 12177