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.
Commins
S P
SP
Departments of Medicine and Biochemistry and Molecular Biology, Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Watson
P M
PM
Levin
N
N
Beiler
R J
RJ
Gettys
T W
TW
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