title: Insulin-like growth factor 1-mediated hyperthermia involves anterior hypothalamic insulin receptors.
abstract: The objective is to investigate the role of insulin-like growth factor 1 (IGF-1) in the regulation of core body temperature. Sequencing cDNA libraries from individual warm-sensitive neurons from the preoptic area (POA) of the hypothalamus, a region involved in the central control of thermoregulation, identified neurons that express both IGF-1 receptor (IGF-1R) and insulin receptor transcripts. The effects of administration of IGF-1 into the POA was measured by radiotelemetry monitoring of core temperature, brown adipose tissue (BAT) temperature, metabolic assessment, and imaging of BAT by positron emission tomography of 2-[(18)F]fluoro-2-deoxyglucose uptake combined with computed tomography. IGF-1 injection into the POA caused dose-dependent hyperthermia that could be blocked by pretreatment with the IGF-1R tyrosine kinase inhibitor, PQ401. The IGF-1-evoked hyperthermia involved activation of brown adipose tissue and was accompanied by a switch from glycolysis to fatty acid oxidation as a source of energy as shown by lowered respiratory exchange ratio. Transgenic mice that lack neuronal insulin receptor expression in the brain (NIRKO mice) were unable to mount the full hyperthermic response to IGF-1, suggesting that the IGF-1 mediated hyperthermia is partly dependent on expression of functional neuronal insulin receptors. These data indicate a novel thermoregulatory role for both IGF-1R and neuronal insulin receptors in IGF-1 activation of BAT and hyperthermia. These central effects of IGF-1 signaling may play a role in regulation of metabolic rate, aging, and the risk of developing type 2 diabetes.
authors.affiliation: Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sanchez-Alavez
authors.forename: Olivia
authors.initials: O
authors.lastname: Osborn
authors.forename: Iustin V
authors.initials: IV
authors.lastname: Tabarean
authors.forename: Kristina H
authors.initials: KH
authors.lastname: Holmberg
authors.forename: James
authors.initials: J
authors.lastname: Eberwine
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Kahn
authors.forename: Tamas
authors.initials: T
authors.lastname: Bartfai
mesh_terms: D000818:Animals; D001833:Body Temperature Regulation; D001921:Brain / Q000378:metabolism; D005334:Fever / Q000209:etiology*; D007032:Hypothalamus, Anterior / Q000737:chemistry*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin / Q000502:physiology*; D015398:Signal Transduction
chemical_list: C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin