title: Fto immunoreactivity is widespread in the rodent brain and abundant in feeding-related sites, but the number of Fto-positive cells is not affected by changes in energy balance.
abstract: A single nucleotide polymorphism in the FTO gene is associated with obesity in humans. Evidence gathered in animals mainly relates energy homeostasis to the central FTO mRNA levels, but our knowledge of the Fto protein distribution and regulation is limited. Fto, a demethylase and transcriptional coactivator, is thought to regulate expression of other genes. Herein, we examined Fto immunoreactivity (IR) in the mouse and rat brain with emphasis on sites governing energy balance. We also studied whether energy status affects central Fto IR. We report that Fto IR, limited to nuclear profiles, is widespread in the brain, in- and outside feeding circuits; it shows a very similar distribution in feeding-related sites in mice and rats. Several areas regulating energy homeostasis display enhanced intensity of Fto staining: the arcuate, paraventricular, supraoptic, dorsomedial, ventromedial nuclei, and dorsal vagal complex. Some regions mediating feeding reward, including the bed nucleus of the stria terminalis, have ample Fto IR. We found that differences in energy status between rats fed ad libitum, deprived or refed following deprivation, did not affect the number of Fto-positive nuclei in 10 sites governing consumption for energy or reward. We conclude that Fto IR, widespread in the rodent brain, is particularly abundant in feeding circuits, but the number of Fto-positive neurons is unaffected by changes in energy balance.
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala, Sweden. olsze005@umn.edu
authors.forename: Pawel K
authors.initials: PK
authors.lastname: Olszewski
authors.forename: Katarzyna J
authors.initials: KJ
authors.lastname: Radomska
authors.forename: Kedar
authors.initials: K
authors.lastname: Ghimire
authors.forename: Anica
authors.initials: A
authors.lastname: Klockars
authors.forename: Caroline
authors.initials: C
authors.lastname: Ingman
authors.forename: Agnieszka M
authors.initials: AM
authors.lastname: Olszewska
authors.forename: Robert
authors.initials: R
authors.lastname: Fredriksson
authors.forename: Allen S
authors.initials: AS
authors.lastname: Levine
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000818:Animals; D001921:Brain / Q000033:anatomy & histology* / Q000378:metabolism* / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D006899:Mixed Function Oxygenases; D009474:Neurons / Q000378:metabolism*; D007652:Oxo-Acid-Lyases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006899:Mixed Function Oxygenases; C524916:FTO protein, mouse; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D007652:Oxo-Acid-Lyases