title: Leptin action through hypothalamic nitric oxide synthase-1-expressing neurons controls energy balance.
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.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Leshan
authors.forename: Megan
authors.initials: M
authors.lastname: Greenwald-Yarnell
authors.forename: Christa M
authors.initials: CM
authors.lastname: Patterson
authors.forename: Ian E
authors.initials: IE
authors.lastname: Gonzalez
authors.forename: Martin G
authors.initials: MG
authors.lastname: Myers
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D007031:Hypothalamus / Q000502:physiology*; D020738:Leptin / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000502:physiology*; D054411:Receptors, Leptin / Q000502:physiology
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse