CNS-Insuin-Res · How insulin resistance in the dorsal vagal complex affects glucose metabolism and feeding behaviour

How insulin resistance in the dorsal vagal complex affects glucose metabolism and feeding behaviour

The Dorsal Vagal Complex (DVC) is an area on the brain that can sense changes in the levels of circulating hormones like insulin, GLP1(Glucagon-Like peptide), glucagon, etc. The DVC can respond to these changes by regulating the way in which we eat, and also by controlling the way in which the liver release glucose in the blood. Altogether these events can regulate the food intake, body weight and blood glucose levels. We are interested in understanding how the DVC senses insulin to regulated feeding behavior, body weight, and blood glucose levels and we try to understand what happened when this part of the brain is not able to respond to insulin. With obesity and type 2 diabetes, in fact, the brain stops sensing insulin and its ability to regulate metabolic functions like food intake body weight and glucose levels are lost. Understanding the molecular mechanism that triggers insulin resistance in the brain could be and important step in developing new treatments to counteract obesity and diabetes. The mitochondria are important organelles presents in every cell and are responsible for producing energy. They work hard and become big by fusing together (mitochondria fusion) when we are in need of energy and they work less and become small (Mitochondria fission) when we have too much energy. We discovered that giving rodent a diet rich in fat for as short as 3 days is sufficient to cause insulin resistance in the DVC and prevent insulin to regulate feeding behavior and blood glucose levels. This loss of insulin sensitivity is due to the fact that the mitochondria become smaller and less active (increase in mitochondria fission). In this fellowship, we aimed to: WP1) Identify the molecular mechanism by which HFD-dependent mitochondria fission causes insulin resistance in the DVC and deregulation of glucose metabolism WP2) Understand whether the increase of mitochondria fission in the DVC can affect the feeding behaviour of the rodent WP3) Identify the neuronal networks involved in the DVC-insulin–dependent regulation of HGP and feeding behaviour.

Data: CORDIS, © European Union