The effect of fasting on the neuronal Fto expression and intracellular localisation in rat brain

Abstract

Fat mass and obesity associated protein (Fto) is a nucleic acid demethylase, which according to the recent structural data exhibits preference for thymine and uracil. This suggests that methylated single-stranded RNA, rather than DNA, may be primary Fto substrate. Fto is abundantly expressed in all hypothalamic sites governing feeding behaviour. Considering that selective modulation of Fto levels in the hypothalamus can influence food intake, we examined the effect of 48 h fasting on the Fto expression in various brain regions. 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 expression and intracellular localization was not observed in neurons of arcuate nucleus, cortex and hippocampus. Our findings suggest that fasting does not universally affect Fto in all the examined brain regions. Both Fto mRNA and catechol-O-methyltransferaze mRNA were upregulated in the identical time-dependent manner in the hypothalamus of 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.