Effect of fasting on the neuronal Fto expression and intracellular localization in the rat brain (959.6)

Abstract

Fat mass and obesity associated protein (Fto) is a nucleic acid demethylase which exhibits preference for thymine and uracil. This suggests that methylated single‐stranded RNA, rather than DNA, may be the primary Fto substrate. Fto is expressed in myriad of tissues, but the expression is especially high in the hypothalamic regions regulating energy homeostasis.Since Fto expression is bidirectionally regulated, as a function of nutritional status, our aim was to examine the effect of 48 h fasting on the Fto expression in various brain regions.qPCR and Western blot were used to assess the Fto mRNA and protein expression respectively. Immunofluorescence was employed to address Fto intracellular localisation.Fasting upregulated overall hypothalamic Fto mRNA and protein expression. More importantly, it was documented for the first time that majority of the enzyme was localized outside cell nuclei in some neurons of paraventricular, ventromedial nucleus and lateral hypothalamic area. Change in the Fto intracellular localization was not observed in neurons of arcuate nucleus, cortex and hippocampus.Although fasting increased hypothalamic Fto content, it did not universally affect Fto expression and intracellular localization in this brain region.Grant Funding Source: Supported by the Serbian Ministry of Education, Science and Technological Development Grant No 17302