title: Fasting induced cytoplasmic Fto expression in some neurons of rat hypothalamus.
abstract: Fat mass and obesity associated protein (Fto) is a nucleic acid demethylase, with a preference for thymine or uracil, according to the recent structural data. This fact suggests that methylated single-stranded RNA, rather than DNA, may be the primary Fto substrate. Fto is abundantly expressed in all hypothalamic sites governing feeding behavior. Considering that selective modulation of Fto levels in the hypothalamus can influence food intake, we set out to investigate the effect of 48 h fasting on the Fto expression in lateral hypothalamic area, paraventricular, ventromedial and arcuate nucleus, the regulatory centres of energy homeostasis. We have demonstrated that 48 h fasting causes not only an increase in the overall hypothalamic levels of both Fto mRNA and protein, but also alters Fto intracellular distribution. This switch happens in some neurons of paraventricular and ventromedial nucleus, as well as lateral hypothalamic area, resulting in the majority of the enzyme being localized outside the cell nuclei. Interestingly, the change in the Fto intracellular localization was not observed in neurons of arcuate nucleus, suggesting that fasting did not universally affect Fto in all of the hypothalmic sites involved in energy homeostasis regulation. Both Fto mRNA and catechol-O-methyltransferaze mRNA were upregulated in the identical time-dependent manner in fasting animals. This fact, combined with the knowledge of the Fto substrate preference, may provide further insight into monoamine metabolism in the state of disturbed energy homeostasis.
authors.affiliation: Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Belgrade, Serbia. predragv@bio.bg.ac.rs
authors.forename: Predrag
authors.initials: P
authors.lastname: Vujovic
authors.forename: Stefan
authors.initials: S
authors.lastname: Stamenkovic
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Jasnic
authors.forename: Iva
authors.initials: I
authors.lastname: Lakic
authors.forename: Sinisa F
authors.initials: SF
authors.lastname: Djurasevic
authors.forename: Gordana
authors.initials: G
authors.lastname: Cvijic
authors.forename: Jelena
authors.initials: J
authors.lastname: Djordjevic
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000818:Animals; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D004734:Energy Metabolism; D005215:Fasting / Q000502:physiology; D005508:Food Deprivation; D015870:Gene Expression; D005786:Gene Expression Regulation; D006706:Homeostasis; D007031:Hypothalamus / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D021381:Protein Transport; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C529321:FTO protein, rat; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase