The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry

@article{Hess2013TheFM,
  title={The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry},
  author={Martin E. Hess and Simon Hess and Kate D. Meyer and Linda A. W. Verhagen and Linda Koch and Hella S. Br{\"o}nneke and Marcelo O. Dietrich and Sabine D. Jordan and Yogesh Saletore and Olivier Elemento and Bengt F. Belgardt and Thomas Franz and Tamas L. Horvath and Ulrich R{\"u}ther and Samie R. Jaffrey and Peter Kloppenburg and Jens C. Br{\"u}ning},
  journal={Nature Neuroscience},
  year={2013},
  volume={16},
  pages={1042-1048}
}
Dopaminergic (DA) signaling governs the control of complex behaviors, and its deregulation has been implicated in a wide range of diseases. Here we demonstrate that inactivation of the Fto gene, encoding a nucleic acid demethylase, impairs dopamine receptor type 2 (D2R) and type 3 (D3R) (collectively, 'D2-like receptor')-dependent control of neuronal activity and behavioral responses. Conventional and DA neuron–specific Fto knockout mice show attenuated activation of G protein–coupled inwardly… 

The Fat Mass and Obesity-Associated Protein (FTO) Regulates Locomotor Responses to Novelty via D2R Medium Spiny Neurons.

Fat mass and obesity-associated (FTO) protein regulates adult neurogenesis.

It is shown that FTO is expressed in adult neural stem cells and neurons and displays dynamic expression during postnatal neurodevelopment and this results suggest FTO plays important roles in neurogenesis, as well as in learning and memory.

Fto in the hippocampus mediates depression-like behaviors

It is reported that expression of the fat mass and obesity associated gene (FTO), a primary RNA demethylase, is downregulated in the hippocampi of both major depressive disorder (MDD) patients and mouse models of depression.

An Obesity-Predisposing Variant of the FTO Gene Regulates D2R-Dependent Reward Learning

It is demonstrated that gene variants of FTO affect dopamine-dependent midbrain brain responses to reward learning and behavioral responses associated with learning from negative outcome in humans during a reward learning task, suggesting a mechanism by which genetic vulnerability in reward processing can increase predisposition to obesity.

Fat mass and obesity-associated protein regulates RNA methylation associated with depression-like behavior in mice

It is reported that expression of the fat mass and obesity associated gene (FTO) is downregulated in the hippocampus of patients with MDD and mouse models of depression, suggesting that FTO is a regulator of a mechanism underlying depression-like behavior in mice.

Valproate-Induced Epigenetic Upregulation of Hypothalamic Fto Expression Potentially Linked with Weight Gain

It is shown that VPA increases the Fto mRNA and protein expression in mouse hypothalamic GT1-7 cells, suggesting an involvement of VPA in the epigenetic upregulation of hypothalamic FTO expression that is potentially associated with the VPA-induced weight gain.

Hypomorphism of Fto and Rpgrip1l causes obesity in mice.

The results of this study indicate that the effects of FTO-associated SNPs on energy homeostasis are due in part to the results of these genetic variations on hypothalamic FTO, RPGRIP1L, and possibly other genes.

Changes in Gene Expression Associated with FTO Overexpression in Mice

The results indicate an upregulation of anabolic pathways and a downregulation of catabolic pathways in FTO-4 mice and no effect of FTO overexpression on m6A methylation of total mRNA was detected.

Erasing m6A-dependent transcription signature of stress-sensitive genes triggers antidepressant actions

The Demethylase Activity of FTO (Fat Mass and Obesity Associated Protein) Is Required for Preadipocyte Differentiation

It is demonstrated that FTO is functionally required for 3T3-L1 differentiation, and treatment with Rosiglitazone, a PPARγ agonist, could overcome the differentiation inhibition imposed by R96Q mutant, suggesting the effect of Fto is mediated through PParγ.
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