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FTO Is Expressed in Neurones throughout the Brain and Its Expression Is Unaltered by Fasting

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 alon...

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Autores principales: McTaggart, James S., Lee, Sheena, Iberl, Michaela, Church, Chris, Cox, Roger D., Ashcroft, Frances M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227617/
https://www.ncbi.nlm.nih.gov/pubmed/22140494
http://dx.doi.org/10.1371/journal.pone.0027968
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author McTaggart, James S.
Lee, Sheena
Iberl, Michaela
Church, Chris
Cox, Roger D.
Ashcroft, Frances M.
author_facet McTaggart, James S.
Lee, Sheena
Iberl, Michaela
Church, Chris
Cox, Roger D.
Ashcroft, Frances M.
author_sort McTaggart, James S.
collection PubMed
description 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.
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spelling pubmed-32276172011-12-02 FTO Is Expressed in Neurones throughout the Brain and Its Expression Is Unaltered by Fasting McTaggart, James S. Lee, Sheena Iberl, Michaela Church, Chris Cox, Roger D. Ashcroft, Frances M. PLoS One Research Article 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. Public Library of Science 2011-11-30 /pmc/articles/PMC3227617/ /pubmed/22140494 http://dx.doi.org/10.1371/journal.pone.0027968 Text en McTaggart et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
McTaggart, James S.
Lee, Sheena
Iberl, Michaela
Church, Chris
Cox, Roger D.
Ashcroft, Frances M.
FTO Is Expressed in Neurones throughout the Brain and Its Expression Is Unaltered by Fasting
title FTO Is Expressed in Neurones throughout the Brain and Its Expression Is Unaltered by Fasting
title_full FTO Is Expressed in Neurones throughout the Brain and Its Expression Is Unaltered by Fasting
title_fullStr FTO Is Expressed in Neurones throughout the Brain and Its Expression Is Unaltered by Fasting
title_full_unstemmed FTO Is Expressed in Neurones throughout the Brain and Its Expression Is Unaltered by Fasting
title_short FTO Is Expressed in Neurones throughout the Brain and Its Expression Is Unaltered by Fasting
title_sort fto is expressed in neurones throughout the brain and its expression is unaltered by fasting
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227617/
https://www.ncbi.nlm.nih.gov/pubmed/22140494
http://dx.doi.org/10.1371/journal.pone.0027968
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