Leptin action through hypothalamic nitric oxide synthase-1-expressing neurons controls energy balance.
Nat Med
; 18(5): 820-3, 2012 May.
Article
em En
| MEDLINE
| ID: mdl-22522563
ABSTRACT
Few effective measures exist to combat the worldwide obesity epidemic(1), and the identification of potential therapeutic targets requires a deeper understanding of the mechanisms that control energy balance. Leptin, an adipocyte-derived hormone that signals the long-term status of bodily energy stores, acts through multiple types of leptin receptor long isoform (LepRb)-expressing neurons (called here LepRb neurons) in the brain to control feeding, energy expenditure and endocrine function(2-4). The modest contributions to energy balance that are attributable to leptin action in many LepRb populations(5-9) suggest that other previously unidentified hypothalamic LepRb neurons have key roles in energy balance. Here we examine the role of LepRb in neuronal nitric oxide synthase (NOS1)-expressing LebRb (LepRb(NOS1)) neurons that comprise approximately 20% of the total hypothalamic LepRb neurons. Nos1(cre)-mediated genetic ablation of LepRb (Lepr(Nos1KO)) in mice produces hyperphagic obesity, decreased energy expenditure and hyperglycemia approaching that seen in whole-body LepRb-null mice. In contrast, the endocrine functions in Lepr(Nos1KO) mice are only modestly affected by the genetic ablation of LepRb in these neurons. Thus, hypothalamic LepRb(NOS1) neurons are a key site of action of the leptin-mediated control of systemic energy balance.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leptina
/
Metabolismo Energético
/
Óxido Nítrico Sintase Tipo I
/
Hipotálamo
/
Neurônios
Limite:
Animals
Idioma:
En
Revista:
Nat Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos