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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.

Fasting Induced Cytoplasmic Fto expression in Some Neurons of Rat Hypothalamus