Neuronal PTP1B regulates body weight, adiposity and leptin action.
Nat Med
; 12(8): 917-24, 2006 Aug.
Article
em En
| MEDLINE
| ID: mdl-16845389
ABSTRACT
Obesity is a major health problem and a risk factor for type 2 diabetes. Leptin, an adipocyte-secreted hormone, acts on the hypothalamus to inhibit food intake and increase energy expenditure. Most obese individuals develop hyperleptinemia and leptin resistance, limiting the therapeutic efficacy of exogenously administered leptin. Mice lacking the tyrosine phosphatase PTP1B are protected from diet-induced obesity and are hypersensitive to leptin, but the site and mechanism for these effects remain controversial. We generated tissue-specific PTP1B knockout (Ptpn1(-/-)) mice. Neuronal Ptpn1(-/-) mice have reduced weight and adiposity, and increased activity and energy expenditure. In contrast, adipose PTP1B deficiency increases body weight, whereas PTP1B deletion in muscle or liver does not affect weight. Neuronal Ptpn1(-/-) mice are hypersensitive to leptin, despite paradoxically elevated leptin levels, and show improved glucose homeostasis. Thus, PTP1B regulates body mass and adiposity primarily through actions in the brain. Furthermore, neuronal PTP1B regulates adipocyte leptin production and probably is essential for the development of leptin resistance.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peso Corporal
/
Regulação Enzimológica da Expressão Gênica
/
Tecido Adiposo
/
Proteínas Tirosina Fosfatases
/
Leptina
/
Neurônios
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Nat Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos