Central leptin regulates the UCP1 and ob genes in brown and white adipose tissue via different beta-adrenoceptor subtypes.
J Biol Chem
; 275(42): 33059-67, 2000 Oct 20.
Article
em En
| MEDLINE
| ID: mdl-10938091
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Propranolol
/
Transcrição Gênica
/
Tecido Adiposo Marrom
/
Proteínas de Transporte
/
Ventrículos Cerebrais
/
Tecido Adiposo
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Regulação da Expressão Gênica
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Leptina
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Receptores Adrenérgicos beta 3
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Proteínas de Membrana
Limite:
Animals
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article