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.

Original publication

DOI

10.1371/journal.pone.0097162

Type

Journal article

Journal

PLoS One

Publication Date

2014

Volume

9

Keywords

Adiposity, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Animals, Cells, Cultured, Gene Expression, Mice, Mice, Inbred C57BL, Mixed Function Oxygenases, Muscle, Skeletal, Obesity, Oxo-Acid-Lyases, Polymorphism, Single Nucleotide