title: Adult NG2-Glia Are Required for Median Eminence-Mediated Leptin Sensing and Body Weight Control.
abstract: While leptin is a well-known regulator of body fat mass, it remains unclear how circulating leptin is sensed centrally to maintain energy homeostasis. Here we show that genetic and pharmacological ablation of adult NG2-glia (also known as oligodendrocyte precursors), but not microglia, leads to primary leptin resistance and obesity in mice. We reveal that NG2-glia contact the dendritic processes of arcuate nucleus leptin receptor (LepR) neurons in the median eminence (ME) and that these processes degenerate upon NG2-glia elimination, which explains the consequential attenuation of these neurons' molecular and electrical responses to leptin. Our data therefore indicate that LepR dendrites in the ME represent the principal conduits of leptin's anorexigenic action and that NG2-glia are essential for their maintenance. Given that ME-directed X-irradiation confirmed the pharmacological and genetically mediated ablation effects on body weight, our findings provide a rationale for the known obesity risk associated with cranial radiation therapy.
authors.affiliation: Department of Medicine, McGill University Health Center Research Institute, McGill University, Montreal, QC H4A 3J1, Canada.
authors.forename: Tina
authors.initials: T
authors.lastname: Djogo
authors.affiliation: Department of Medicine, McGill University Health Center Research Institute, McGill University, Montreal, QC H4A 3J1, Canada.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Robins
authors.affiliation: Physiological Genomics, Institute of Physiology, Ludwig Maximilians University Munich, 80336 Munich, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schneider
authors.affiliation: Department of Medicine, McGill University Health Center Research Institute, McGill University, Montreal, QC H4A 3J1, Canada.
authors.forename: Darya
authors.initials: D
authors.lastname: Kryzskaya
authors.affiliation: Department of Medicine, McGill University Health Center Research Institute, McGill University, Montreal, QC H4A 3J1, Canada.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Medicine, McGill University Health Center Research Institute, McGill University, Montreal, QC H4A 3J1, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mingay
authors.affiliation: Department of Medicine, McGill University Health Center Research Institute, McGill University, Montreal, QC H4A 3J1, Canada.
authors.forename: Colleen J
authors.initials: CJ
authors.lastname: Gillon
authors.affiliation: Department of Medicine, McGill University Health Center Research Institute, McGill University, Montreal, QC H4A 3J1, Canada.
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, QC H4H 1R3, Canada.
authors.forename: Kai-Florian
authors.initials: KF
authors.lastname: Storch
authors.affiliation: Department of Pharmacology and Toxicology, University of Saarland School of Medicine, 66421 Homburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Boehm
authors.affiliation: Centre for Research in Neuroscience, Montreal General Hospital, McGill University, Montreal, QC H3G 1A4, Canada.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Bourque
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Stroh
authors.affiliation: Physiological Genomics, Institute of Physiology, Ludwig Maximilians University Munich, 80336 Munich, Germany.
authors.forename: Leda
authors.initials: L
authors.lastname: Dimou
authors.affiliation: Department of Medicine, McGill University Health Center Research Institute, McGill University, Montreal, QC H4A 3J1, Canada. Electronic address: maia.kokoeva@mcgill.ca.
authors.forename: Maia V
authors.initials: MV
authors.lastname: Kokoeva
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000855:Anorexia / Q000378:metabolism; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005260:Female; D017353:Gene Deletion; D020738:Leptin / Q000378:metabolism*; D008297:Male; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D009457:Neuroglia / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D054411:Receptors, Leptin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D003561:Cytarabine