title: Hypothalamic reactive oxygen species are required for insulin-induced food intake inhibition: an NADPH oxidase-dependent mechanism.
abstract: OBJECTIVE
  Insulin plays an important role in the hypothalamic control of energy balance, especially by reducing food intake. Emerging data point to a pivotal role of reactive oxygen species (ROS) in energy homeostasis regulation, but their involvement in the anorexigenic effect of insulin is unknown. Furthermore, ROS signal derived from NADPH oxidase activation is required for physiological insulin effects in peripheral cells. In this study, we investigated the involvement of hypothalamic ROS and NADPH oxidase in the feeding behavior regulation by insulin.
  
  
  METHODS
  We first measured hypothalamic ROS levels and food intake after acute intracerebroventricular injection of insulin. Second, effect of pretreatment with a ROS scavenger or an NADPH oxidase inhibitor was evaluated. Third, we examined the consequences of two nutritional conditions of central insulin unresponsiveness (fasting or short-term high-fat diet) on the ability of insulin to modify ROS level and food intake.
  
  
  RESULTS
  In normal chow-fed mice, insulin inhibited food intake. At the same dose, insulin rapidly and transiently increased hypothalamic ROS levels by 36%. The pharmacological suppression of this insulin-stimulated ROS elevation, either by antioxidant or by an NADPH oxidase inhibitor, abolished the anorexigenic effect of insulin. Finally, in fasted and short-term high-fat diet-fed mice, insulin did not promote elevation of ROS level and food intake inhibition, likely because of an increase in hypothalamic diet-induced antioxidant defense systems.
  
  
  CONCLUSIONS
  A hypothalamic ROS increase through NADPH oxidase is required for the anorexigenic effect of insulin.
authors.affiliation: Université de Toulouse, UPS, UMR 5241 Métabolisme, Plasticité et Mitochondrie, Toulouse, France.
authors.forename: Tristan
authors.initials: T
authors.lastname: Jaillard
authors.forename: Michael
authors.initials: M
authors.lastname: Roger
authors.forename: Anne
authors.initials: A
authors.lastname: Galinier
authors.forename: Pascale
authors.initials: P
authors.lastname: Guillou
authors.forename: Alexandre
authors.initials: A
authors.lastname: Benani
authors.forename: Corinne
authors.initials: C
authors.lastname: Leloup
authors.forename: Louis
authors.initials: L
authors.lastname: Casteilla
authors.forename: Luc
authors.initials: L
authors.lastname: Pénicaud
authors.forename: Anne
authors.initials: A
authors.lastname: Lorsignol
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D002149:Energy Intake / Q000187:drug effects / Q000502:physiology*; D004734:Energy Metabolism; D005978:Glutathione / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000502:physiology*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D005978:Glutathione