Changes in gene expression associated with FTO overexpression in mice

PLoS One. 2014 May 19;9(5):e97162. doi: 10.1371/journal.pone.0097162. eCollection 2014.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Mixed Function Oxygenases
  • FTO protein, mouse
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Oxo-Acid-Lyases