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Leptin action through hypothalamic nitric oxide synthase-1-expressing neurons controls energy balance.

Nature medicine | 2012

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.

Pubmed ID: 22522563 RIS Download

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Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: DK057768
  • Agency: NIGMS NIH HHS, United States
    Id: T32GM008322
  • Agency: NHLBI NIH HHS, United States
    Id: T32 HL007853
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK057768-13
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK057768
  • Agency: NIDDK NIH HHS, United States
    Id: P60 DK020572-35
  • Agency: NINDS NIH HHS, United States
    Id: T32 NS076401
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM008322
  • Agency: NIDDK NIH HHS, United States
    Id: P60 DK020572
  • Agency: NHLBI NIH HHS, United States
    Id: T32HL007853
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK020572

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