The molecular, cellular and circuit changes involved in the metabolic-olfactory feedback loop

我们的嗅觉因饥饿而增强，因食物消耗而受到抑制。当饥饿时，气味更容易察觉，食物的气味看起来更令人愉快，刺激食物消费。相反，当能量水平高时，气味敏感性降低。令人惊讶的是，嗅觉在新陈代谢中起着更大的作用;例如，糖尿病的风险因素，如脂肪量，胰岛素敏感性和食物消耗都受到嗅觉的影响。我们还不知道处理气味的大脑回路是如何影响这些代谢因素的。这些知识可能会导致针对嗅觉的新疗法，以改善代谢健康。肥胖和糖尿病是可预防死亡的主要原因，成人和儿童的死亡率都在上升。因此，任何能够降低这些代谢紊乱发生率的治疗方法都将带来重大的健康、社会和经济效益。该项目将使用尖端技术来揭示大脑处理气味区域中发生的代谢诱导回路变化。将确定这种调节发生的分子机制，然后使用最先进的技术，我们将确定靶向所确定分子的药物是否可用作改善代谢健康的疗法。

Our sense of smell is heightened by hunger and suppressed by food consumption. When hungry, odours are easier to detect and food odours appear more pleasant, stimulating food consumption. Conversely, when energy levels are high, odour sensitivity is lowered. Surprisingly the sense of smell plays a larger role in metabolism; for example, diabetic risk factors such as fat mass, insulin sensitivity and food consumption are affected by the sense of smell. We do not yet understand how the brain circuits involved in processing odours influence such metabolic factors. Such knowledge could lead to novel therapies that target the sense of smell to improve metabolic health. Obesity and diabetes are leading causes of preventable death with the rates increasing in adults as well as children. Therefore, any therapy that can reduce the rates of these metabolic disorders will have major health, societal and economic benefits.This project will use cutting-edge techniques to reveal the metabolic-induced circuit changes occurring in the the brain region that process odours. The molecular mechanisms through which this modulation occurs will be identified, then using state-of-the-art technology we will determine whether drugs that target the identified molecules will prove useful as therapies to improve metabolic health.