Adrenalectomy after weaning restores beta3-adrenergic receptor expression in white adipocytes from C57BL/6J-ob/ob mice.
The role of hypercorticism in the development of compromised beta-adrenergic signaling in adipose tissue was assessed in ob/ob mice adrenalectomized at 4 weeks of age and studied 1 and 3 weeks thereafter. Adrenalectomy prevented the rapid increase in body weight and fat deposition between 4 and 5 weeks of age in ob/ob mice and produced a phenotype indistinguishable from that of lean mice. However, adrenalectomized ob/ob mice became intermediate between lean and ob/ob mice by 7 weeks of age. Adipocyte beta3-adrenergic receptor (AR) messenger RNA levels were similar between lean and adrenalectomized ob/ob mice at both time points and were 4- to 8-fold higher than messenger RNA levels in ob/ob mice. As judged by maximal activation of adenylyl cyclase by a beta3-AR-selective agonist, adrenalectomy also restored functional activity of the beta3-AR to levels above or equivalent to those seen in lean mice at both time points. The present results suggest that development of hypercorticism at or before weaning in ob/ob mice represses expression of the beta3-AR and prevents the normal postweaning development of this signaling system in the adipocyte.
Gettys
T W
TW
Department of Medicine, Medical University of South Carolina, Charleston 29425, USA. Gettystw@musc.edu
Watson
P M
PM
Seger
L
L
Padgett
M
M
Taylor
I L
IL
D017667:Adipocytes / Q000378:metabolism*; D000311:Adrenal Glands / Q000502:physiology*; D000315:Adrenalectomy; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D000242:Cyclic AMP / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D012333:RNA, Messenger / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000235:genetics* / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3; D012260:Ribonucleases / Q000378:metabolism; D015398:Signal Transduction; D013237:Stereoisomerism; D014886:Weaning
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004149:Dioxoles; D007093:Imidazoles; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; C049763:CGP 20712A; D000242:Cyclic AMP; D012260:Ribonucleases; D004837:Epinephrine