title: Glut2-dependent glucose-sensing controls thermoregulation by enhancing the leptin sensitivity of NPY and POMC neurons.
abstract: The physiological contribution of glucose in thermoregulation is not completely established nor whether this control may involve a regulation of the melanocortin pathway. Here, we assessed thermoregulation and leptin sensitivity of hypothalamic arcuate neurons in mice with inactivation of glucose transporter type 2 (Glut2)-dependent glucose sensing. Mice with inactivation of Glut2-dependent glucose sensors are cold intolerant and show increased susceptibility to food deprivation-induced torpor and abnormal hypothermic response to intracerebroventricular administration of 2-deoxy-d-glucose compared to control mice. This is associated with a defect in regulated expression of brown adipose tissue uncoupling protein I and iodothyronine deiodinase II and with a decreased leptin sensitivity of neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons, as observed during the unfed-to-refed transition or following i.p. leptin injection. Sites of central Glut-2 expression were identified by a genetic tagging approach and revealed that glucose-sensitive neurons were present in the lateral hypothalamus, the dorsal vagal complex, and the basal medulla but not in the arcuate nucleus. NPY and POMC neurons were, however, connected to nerve terminals from Glut2-expressing neurons. Thus, our data suggest that glucose controls thermoregulation and the leptin sensitivity of NPY and POMC neurons through activation of Glut2-dependent glucose-sensing neurons located outside of the arcuate nucleus.
authors.affiliation: Department of Physiology and Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Mounien
authors.forename: Nell
authors.initials: N
authors.lastname: Marty
authors.forename: David
authors.initials: D
authors.lastname: Tarussio
authors.forename: Salima
authors.initials: S
authors.lastname: Metref
authors.forename: David
authors.initials: D
authors.lastname: Genoux
authors.forename: Frédéric
authors.initials: F
authors.lastname: Preitner
authors.forename: Marc
authors.initials: M
authors.lastname: Foretz
authors.forename: Bernard
authors.initials: B
authors.lastname: Thorens
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001833:Body Temperature Regulation; D005260:Female; D005947:Glucose / Q000032:analysis / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000502:physiology*; D006801:Humans; D007124:Immunoenzyme Techniques; D019426:Integrases; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071256:Uncoupling Protein 1; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D005947:Glucose; D051273:Glucose Transporter Type 2; D019426:Integrases; D007453:Iodide Peroxidase; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; D009478:Neuropeptide Y; D011333:Pro-Opiomelanocortin; D012333:RNA, Messenger; D000071256:Uncoupling Protein 1; D000097564:Iodothyronine Deiodinase Type II; C495682:Slc2a2 protein, mouse; C045073:Cre recombinase