title: Haematopoietic cells produce BDNF and regulate appetite upon migration to the hypothalamus.
abstract: Brain-derived neurotrophic factor (BDNF) suppresses food intake by acting on neurons in the hypothalamus. Here we show that BDNF-producing haematopoietic cells control appetite and energy balance by migrating to the hypothalamic paraventricular nucleus. These haematopoietic-derived paraventricular nucleus cells produce microglial markers and make direct contacts with neurons in response to feeding status. Mice with congenital BDNF deficiency, specifically in haematopoietic cells, develop hyperphagia, obesity and insulin resistance. These abnormalities are ameliorated by bone marrow transplantation with wild-type bone marrow cells. Furthermore, when injected into the third ventricle, wild-type bone marrow mononuclear cells home to the paraventricular nucleus and reverse the hyperphagia of BDNF-deficient mice. Our results suggest a novel mechanism of feeding control based on the production of BDNF by haematopoietic cells and highlight a potential new therapeutic route for the treatment of obesity.
authors: Department of Molecular Genetics in Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
authors: Hiroshi
authors: H
authors: Urabe
authors: Hideto
authors: H
authors: Kojima
authors: Lawrence
authors: L
authors: Chan
authors: Tomoya
authors: T
authors: Terashima
authors: Nobuhiro
authors: N
authors: Ogawa
authors: Miwako
authors: M
authors: Katagi
authors: Kazunori
authors: K
authors: Fujino
authors: Asako
authors: A
authors: Kumagai
authors: Hiromichi
authors: H
authors: Kawai
authors: Akihiro
authors: A
authors: Asakawa
authors: Akio
authors: A
authors: Inui
authors: Hitoshi
authors: H
authors: Yasuda
authors: Yutaka
authors: Y
authors: Eguchi
authors: Kazuhiro
authors: K
authors: Oka
authors: Hiroshi
authors: H
authors: Maegawa
authors: Atsunori
authors: A
authors: Kashiwagi
authors: Hiroshi
authors: H
authors: Kimura
mesh_terms: D000818:Animals; D001066:Appetite / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016026:Bone Marrow Transplantation; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000172:deficiency / Q000378:metabolism / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D004327:Drinking Behavior / Q000187:drug effects; D005215:Fasting / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects; D017353:Gene Deletion; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D006963:Hyperphagia / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D007276:Injections, Intraventricular; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D009928:Organ Specificity / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure
chemical_list: D019208:Brain-Derived Neurotrophic Factor