title: Fto colocalizes with a satiety mediator oxytocin in the brain and upregulates oxytocin gene expression.
abstract: Single nucleotide polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. Alterations in Fto expression in transgenic animals affect body weight, energy expenditure and food intake. Fto, a nuclear protein and proposed transcription co-factor, has been speculated to affect energy balance through a functional relationship with specific genes encoding feeding-related peptides. Herein, we employed double immunohistochemistry and showed that the majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto in the brain of male and female mice. We then overexpressed Fto in a murine hypothalamic cell line and, using qPCR, detected a 50% increase in the level of oxytocin mRNA. Expression levels of several other feeding-related genes, including neuropeptide Y (NPY) and Agouti-related protein (AgRP), were unaffected by the FTO transfection. Addition of 10 and 100 nmol oxytocin to the cell culture medium did not affect Fto expression in hypothalamic cells. We conclude that Fto, a proposed transcription co-factor, influences expression of the gene encoding a satiety mediator, oxytocin.
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: Robert
authors.initials: R
authors.lastname: Fredriksson
authors.forename: Jenny D
authors.initials: JD
authors.lastname: Eriksson
authors.forename: Anaya
authors.initials: A
authors.lastname: Mitra
authors.forename: Katarzyna J
authors.initials: KJ
authors.lastname: Radomska
authors.forename: Blake A
authors.initials: BA
authors.lastname: Gosnell
authors.forename: Maria N
authors.initials: MN
authors.lastname: Solvang
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 / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D006899:Mixed Function Oxygenases; D009474:Neurons / Q000378:metabolism; D007652:Oxo-Acid-Lyases / Q000378:metabolism*; D010121:Oxytocin / Q000235:genetics* / Q000378:metabolism*; D012528:Satiety Response
chemical_list: D010121:Oxytocin; D006899:Mixed Function Oxygenases; C524916:FTO protein, mouse; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D007652:Oxo-Acid-Lyases