INSULIN SENSING IN THE BRAIN AND THE EFFECTS OF INSULIN RESISTANCE ON METABOLIC BEHAVIOUR

到2020年，至少70%的世界人口将超重或肥胖。这些人更有可能是胰岛素抵抗和发展糖尿病。大脑收集来自身体周围的输入，以调节葡萄糖代谢和个体的进食行为，并向外周器官发出信号，以确保平衡的激素反应。这些激素和代谢过程的改变可导致代谢疾病。我发现，大脑中一个名为背迷走神经复合体（DVC）的特定区域可以感知胰岛素，从而调节血糖水平、食物摄入量和体重。我的目标是精确地研究胰岛素信号在DVC和神经元群体参与。DVC失去了对高脂饮食喂养引起的胰岛素水平变化的反应能力。特别是，我发现线粒体动力学的变化可以触发DVC中胰岛素敏感性的丧失，从而导致血糖水平升高和肥胖。我将研究导致DVC中胰岛素抵抗的分子机制以及DVC在引发肥胖和糖尿病中的作用。为此，我将使用肥胖和糖尿病的动物模型，并将研究通过专门针对DVC来改善其疾病状况的方法。

At least 70% of the world population will be overweight or obese by 2020. These individuals are more likely to be insulin resistant and develop diabetes. The brain collects inputs from around the body to regulate glucose metabolism and feeding behaviour of an individual, and signals back to the peripheral organs to ensure a balanced hormonal response. Alteration of these hormonal and metabolic processes can lead to metabolic diseases. I discovered that a specific area of the brain called the Dorsal Vagal Complex (DVC) senses insulin to regulate blood glucose levels, food intake and body weight. I aim to study precisely how insulin signals in the DVC and which neuronal populations are involved. The DVC looses the ability to respond to changes in insulin levels due to high-fat diet feeding. In particular, I discover that changes in mitochondrial dynamics can trigger the loss of insulin sensitivity in the DVC thus causing an increase in blood glucose levels and obesity. I will study the molecular mechanism that causes insulin resistance in the DVC and the role of the DVC in triggering obesity and diabetes. To this aim, I will use animal models of obesity and diabetes and I will look at ways to ameliorate their disease condition by targetting specifically the DVC.