Project 1: Causes of brain insulin resistance

Consuming a high-fat diet containing large amounts of long chain saturated fatty acids induces insulin and leptin resistance in the central nervous system. The pancreas-derived hormone insulin and the adipose tissue-produced hormone leptin act in the brain to reduce food intake and increase energy expenditure.  The causative factors resulting in these hormone resistances are insufficiently resolved, yet these resistances have a major impact on metabolism and cognition. Previously, we have demonstrated that mitochondrial dysfunction and insulin resistance are early events of obesity development. Of note, this dysregulation even associates with certain neurodegenerative diseases.

In this project we investigate, how mitochondria and nutrients, affect neuronal metabolism, insulin sensitivity and energy homeostasis. Furthermore, we examine novel modulators of insulin signaling in the brain using different in vitro and in vivo models. To perform these experiments, we use novel techniques, such as respirometry and live-cell imaging, which allow us to directly assess mitochondrial function within cells before and after insulin treatment or with chronic dietary interventions.