Influence of Age, Biological Sex and Body Weight on Brain Insulin Signalling

Abstract

Insulin is a pancreatic hormone, able to pass the blood-brain barrier (BBB) to act on the central nervous system. Insulin receptors are widely distributed across the brain and found in high densities in regions like the cerebellum, hypothalamus, olfactory bulb, hippocampus, frontal cortex and striatum. Brain insulin signalling plays a crucial role in regulating whole-body metabolism, cognitive processes and eating behaviour. Different factors and conditions, including obesity and ageing, were shown to influence either insulin availability in the brain through changes in the transport across the BBB or by directly influencing brain insulin action. Our studies confirm that insulin signalling in the brain plays an important role in cognitive processes and in the regulation of homeostasis, appetite and reward regulation. Furthermore, our results demonstrate that insulin action is influenced and modulated by obesity, sex and age in a region-specific and task-specific manner.