Journal Article

FTO affects hippocampal function by regulation of BDNF processing

Spychala, André, Rüther, Ulrich

2019

Overview

Initially, the function of the fat mass and obesity associated (Fto) gene seemed to be primarily the regulation of the body weight. Here we show that loss of Fto results in a hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis. In consequence, Fto-/- mice display an anxiety-like behavior and impairments in working memory. Furthermore, differentiation of neurons is affected in the hippocampus. As a cause of these impairments we identified a processing defect of the neurotrophin BDNF which is most likely the result of a reduced expression of MMP-9. Therefore, we propose FTO as a possible new target to develop novel approaches for the treatment of diseases associated with hippocampal disorders. In parallel, we also would like to make the point that any anti-obesity therapy via blocking FTO function can have negative effects on the proper function of the hippocampus.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adrenal glands / Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics / Alpha-Ketoglutarate-Dependent Dioxygenase FTO - metabolism / Animals / Anxiety / Anxiety - genetics / Anxiety - metabolism / Anxiety - pathology / Behavior / Behavior, Animal / Biology and Life Sciences / Body fat / Body weight / Brain / Brain-derived neurotrophic factor / Brain-Derived Neurotrophic Factor - genetics / Brain-Derived Neurotrophic Factor - metabolism / Cell growth / Displays (Marketing) / Gelatinase B / Gene expression / Genes / Genetic aspects / Health aspects / Hippocampus / Hippocampus (Brain) / Hippocampus - metabolism / Hippocampus - pathology / Hypothalamic-pituitary-adrenal axis / Hypothalamo-Hypophyseal System - metabolism / Hypothalamo-Hypophyseal System - pathology / Hypothalamus / Matrix Metalloproteinase 9 - biosynthesis / Matrix Metalloproteinase 9 - genetics / Medical treatment / Medicine and Health Sciences / Memory / Memory Disorders - genetics / Memory Disorders - metabolism / Memory Disorders - pathology / Memory, Short-Term / Mice / Mice, Knockout / Molecular biology / Nervous system / Neurogenesis / Neurons / Obesity / Pituitary / Pituitary-Adrenal System - metabolism / Pituitary-Adrenal System - pathology / Protein Processing, Post-Translational / Short term memory / Social Sciences / Stress / Stress response / Therapeutics