Central leptin regulates the UCP1 and ob genes in brown and white adipose tissue via different beta-adrenoceptor subtypes.
The three known subtypes of beta-adrenoreceptors (beta(1)-AR, beta(2)-AR, and beta(3)-AR) are differentially expressed in brown and white adipose tissue and mediate peripheral responses to central modulation of sympathetic outflow by leptin. To assess the relative roles of the beta-AR subtypes in mediating leptin's effects on adipocyte gene expression, mice with a targeted disruption of the beta(3)-adrenoreceptor gene (beta(3)-AR KO) were treated with vehicle or the beta(1)/beta(2)-AR selective antagonist, propranolol (20 microgram/g body weight/day) prior to intracerebroventricular (ICV) injections of leptin (0.1 microgram/g body weight/day). Leptin produced a 3-fold increase in UCP1 mRNA in brown adipose tissue of wild type (FVB/NJ) and beta(3)-AR KO mice. The response was unaltered by propranolol in wild type mice, but was completely blocked by this antagonist in beta(3)-AR KO mice. In contrast, ICV leptin had no effect on leptin mRNA in either epididymal or retroperitoneal white adipose tissue (WAT) from beta(3)-AR KOs. Moreover, propranolol did not block the ability of exogenous leptin to reduce leptin mRNA in either WAT depot site of wild type mice. These results demonstrate that the beta(3)-AR is required for leptin-mediated regulation of ob mRNA expression in WAT, but is interchangeable with the beta(1)/beta(2)-ARs in mediating leptin's effect on UCP1 mRNA expression in brown adipose tissue.
Departments of Medicine and Biochemistry and Molecular Biology, Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
S P
SP
Commins
P M
PM
Watson
N
N
Levin
R J
RJ
Beiler
T W
TW
Gettys
D000273:Adipose Tissue / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D007473:Ion Channels; D020738:Leptin / Q000008:administration & dosage / Q000235:genetics* / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D024101:Mitochondrial Proteins; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D022702:Receptors, Adrenergic, beta-3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D054411:Receptors, Leptin; D014158:Transcription, Genetic; D000071256:Uncoupling Protein 1
C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D000319:Adrenergic beta-Antagonists; D002352:Carrier Proteins; D007093:Imidazoles; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011412:Propanolamines; D012333:RNA, Messenger; D022702:Receptors, Adrenergic, beta-3; D054411:Receptors, Leptin; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C515447:leptin receptor, mouse; D011433:Propranolol; C049763:CGP 20712A