Lieu : Centre Broca
Brain insulin signaling plays a key role in metabolism and mental health
Andre Kleinridders
German Institute of Human Nutrition
Invité par Xavier Fioramonti (NutriNeuro)
Research focus Group Kleinridders
My research interest aims at understanding causes and consequences of brain insulin resistance particularly with regard to understand the interaction of brain insulin sensitivity and mitochondrial function. We have shown that the consumption of HFD activates the innate immune system, which is instrumental to induce hypothalamic leptin resistance with concomitant insulin resistance. Following, we were able to reveal that type 2 diabetic patients exhibit reduced expression of mitochondrial chaperones in the hypothalamus. The resultant, reduced mitochondrial stress response (MSR) induces brain insulin resistance identifying mitochondrial dysfunction as cause for hypothalamic insulin resistance. Recently, we were able to show that the dysregulation of the MSR is one of the earliest alterations in obesity development and are caused by insulin resistance. Conversely, treating neurons or mice with insulin, increases the expression of MSR genes with protection against diet-induced weight gain. Thus, the dysregulation of the MSR represents a cause and consequence of brain insulin resistance.
We further investigate consequences of brain insulin resistance with a particular focus on emotional behavior. Here we show that neuronal and glia specific deficiency of insulin receptor causes anxiety and depressive-like behavior due to alterations in the dopaminergic system. Currently we investigate mechanisms of acute intranasal insulin on emotional behavior in mice and men and identify acute alterations in the ventral striatum as potential target sites for insulin-induced improvements in emotional behavior.