title: FTO is expressed in neurones throughout the brain and its expression is unaltered by fasting.
abstract: Single-nucleotide polymorphisms in the first intron of the ubiquitously expressed FTO gene are associated with obesity. Although the physiological functions of FTO remain unclear, food intake is often altered when Fto expression levels are manipulated. Furthermore, deletion of FTO from neurones alone has a similar effect on food intake to deletion of FTO in all tissues. These results indicate that FTO expression in the brain is particularly important. Considerable focus has been placed on the dynamic regulation of Fto mRNA expression in the hypothalamus after short-term (16-48 hour) fasting, but results have been controversial. There are no studies that quantify FTO protein levels across the brain, and assess its alteration following short-term fasting. Using immunohistochemistry, we found that FTO protein is widely expressed in mouse brain, and present in the majority of neurones. Using quantitative Western blotting and RT-qPCR we show that FTO protein and mRNA levels in the hypothalamus, cerebellum and rostral brain are relatively uniform, and levels in the brain are higher than in skeletal muscles of the lower limbs. Fasting for 18 hours does not alter the expression pattern, or levels, of FTO protein and mRNA. We further show that the majority of POMC neurones, which are critically involved in food intake regulation, also express FTO, but that the percentage of FTO-positive POMC neurones is not altered by fasting. In summary, we find no evidence that Fto/FTO expression is regulated by short-term (18-hour) fasting. Thus, it is unlikely that the hunger and increased post-fasting food intake caused by such food deprivation is driven by alterations in Fto/FTO expression. The widespread expression of FTO in neurones also suggests that physiological studies of this protein should not be limited to the hypothalamus.
authors.affiliation: Department of Physiology, Anatomy and Genetics, OXION Centre for Ion Channel Studies, Henry Wellcome Centre for Gene Function, Oxford, United Kingdom.
authors.forename: James S
authors.initials: JS
authors.lastname: McTaggart
authors.forename: Sheena
authors.initials: S
authors.lastname: Lee
authors.forename: Michaela
authors.initials: M
authors.lastname: Iberl
authors.forename: Chris
authors.initials: C
authors.lastname: Church
authors.forename: Roger D
authors.initials: RD
authors.lastname: Cox
authors.forename: Frances M
authors.initials: FM
authors.lastname: Ashcroft
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D005215:Fasting / Q000378:metabolism*; D005247:Feeding Behavior / Q000502:physiology; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D006899:Mixed Function Oxygenases; D009474:Neurons / Q000378:metabolism*; D007652:Oxo-Acid-Lyases / Q000235:genetics* / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; D006899:Mixed Function Oxygenases; C524916:FTO protein, mouse; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D007652:Oxo-Acid-Lyases