Jens C Brüning - C 6

Fto-dependent regulation of hypothalamic neurons

Abstract

Variants in the FTO gene exhibit the strongest genetic association with obesity across different ethnicities. Our previous work revealed that Fto in mice controls energy homeostasis, and that it acts as a m6A-RNA demethylase and through this activity regulates dopaminergic signalling not only in mice but also in humans. We have recently identified novel mRNAs, which are targeted by Fto-mediated demethylation in vivo in the hypothalamus, a key regulatory centre of energy and glucose homeostasis. The aim of the current proposal is to define the molecular mechanism through which Fto-dependent regulation of PVH-neurons regulates energy homeostasis to validate novel targets for obesity treatment.

Clinical/medical relevance and sustainability in disease understanding

Obesity represents a major unmet medical need affecting more than 35% of the population. Defining the mechanisms, through which the most frequent genetic variants underlying common obesity contribute to the development of disease will set the ground for urgently needed novel therapeutic strategies. Our previous work on Fto has already revealed important novel insights into the function of Fto in control of dopaminergic signalling, findings, which we could already confirm in translational neuroimaging studies in humans. Targeted therapies for obesity based on these findings are already subject to an investigator-initiated clinical trial. Thus, our strategy to rapidly translate novel molecular mechanisms defined in mouse experiments represents a valid strategy.


Prof. Dr. med. Jens C Brüning

Center for Endocrinology, Diabetology and Prev. Medicine

Prof. Dr. med. Jens Brüning

Principal Investigator C 6 / Exec. Board Member

bruening@sf.mpg.de,

Work +49 221 470 2467

Fax (Work) +49 221 470 5185

Kerpener Str. 62
50937 Cologne

http://zedp.uk-koeln.de/

Publications - Jens C Brüning

Link to PubMed