Changes in gene expression associated with FTO overexpression in mice.
Single nucleotide polymorphisms in the first intron of the fat-mass-and-obesity-related gene FTO are associated with increased body weight and adiposity. Increased expression of FTO is likely underlying this obesity phenotype, as mice with two additional copies of Fto (FTO-4 mice) exhibit increased adiposity and are hyperphagic. FTO is a demethylase of single stranded DNA and RNA, and one of its targets is the m6A modification in RNA, which might play a role in the regulation of gene expression. In this study, we aimed to examine the changes in gene expression that occur in FTO-4 mice in order to gain more insight into the underlying mechanisms by which FTO influences body weight and adiposity. Our results indicate an upregulation of anabolic pathways and a downregulation of catabolic pathways in FTO-4 mice. Interestingly, although genes involved in methylation were differentially regulated in skeletal muscle of FTO-4 mice, no effect of FTO overexpression on m6A methylation of total mRNA was detected.
Henry Wellcome Centre for Gene Function, Department of Physiology, Anatomy; and Genetics, University of Oxford, Parks Road, Oxford, United Kingdom.
Myrte
M
Merkestein
Henry Wellcome Centre for Gene Function, Department of Physiology, Anatomy; and Genetics, University of Oxford, Parks Road, Oxford, United Kingdom.
James S
JS
McTaggart
Henry Wellcome Centre for Gene Function, Department of Physiology, Anatomy; and Genetics, University of Oxford, Parks Road, Oxford, United Kingdom.
Sheena
S
Lee
Henry Wellcome Centre for Gene Function, Department of Physiology, Anatomy; and Genetics, University of Oxford, Parks Road, Oxford, United Kingdom.
Holger B
HB
Kramer
Medical Research Council Harwell, Mammalian Genetics Unit, Harwell Science and Innovation Campus, Harwell, Oxford, United Kingdom.
Fiona
F
McMurray
Henry Wellcome Centre for Gene Function, Department of Physiology, Anatomy; and Genetics, University of Oxford, Parks Road, Oxford, United Kingdom.
Mathilde
M
Lafond
Henry Wellcome Centre for Gene Function, Department of Physiology, Anatomy; and Genetics, University of Oxford, Parks Road, Oxford, United Kingdom.
Lily
L
Boutens
Medical Research Council Harwell, Mammalian Genetics Unit, Harwell Science and Innovation Campus, Harwell, Oxford, United Kingdom.
Roger
R
Cox
Henry Wellcome Centre for Gene Function, Department of Physiology, Anatomy; and Genetics, University of Oxford, Parks Road, Oxford, United Kingdom.
Frances M
FM
Ashcroft
D050154:Adiposity / Q000235:genetics / Q000502:physiology; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression; D051379:Mice; D008810:Mice, Inbred C57BL; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D007652:Oxo-Acid-Lyases / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D006899:Mixed Function Oxygenases; C524916:FTO protein, mouse; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D007652:Oxo-Acid-Lyases