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

Leshan, Rebecca L; Greenwald-Yarnell, Megan; Patterson, Christa M; Gonzalez, Ian E; Myers, Martin G
May 2012
Nature Medicine;May2012, Vol. 18 Issue 5, p820
Academic Journal
Few effective measures exist to combat the worldwide obesity epidemic, 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. The modest contributions to energy balance that are attributable to leptin action in many LepRb populations 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 (LepRbNOS1) neurons that comprise approximately 20% of the total hypothalamic LepRb neurons. Nos1cre-mediated genetic ablation of LepRb (LeprNos1KO) 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 LeprNos1KO mice are only modestly affected by the genetic ablation of LepRb in these neurons. Thus, hypothalamic LepRbNOS1 neurons are a key site of action of the leptin-mediated control of systemic energy balance.


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