Octopamine Mediates Benefits Of Endurance Exercise In Drosophila

摘要 每天锻炼是一种低成本的治疗方法，可以改善新陈代谢健康，防止与年龄有关的疾病。 疾病然而，许多人由于疾病而无法进行耐力锻炼方案， 残疾、高龄或迫使久坐行为的工作时间表。泰勒把文化 他们对运动的反应存在很大的个体差异。导致这种差异的遗传因素不是 很好理解。在这里，我们建议使用果蝇遗传模型系统来确定这一点的原因 方差在这个过程中，我们将确定治疗药物的新靶点， 无法完成锻炼计划的患者的锻炼益处。初步数据显示， 表明运动过程中章鱼胺能神经元的激活对于诱导代谢适应是至关重要的， 肌肉和脂肪。此外，章鱼胺治疗能够诱导运动适应， 久坐的苍蝇在这里，我们将确定哪些受体或受体所需的章鱼胺信号， 这些好处（目标1）。其次，我们将利用运动中的性别差异 研究果蝇对日常运动的反应，以确定导致个体对日常运动反应的遗传差异。 这些结果将1）为诊断的发展提供信息，以预测个人对运动训练的反应， 和2）为治疗提供新的靶点以向久坐患者提供锻炼的益处。

Abstract Daily exercise is a low-cost treatment that improves metabolic health and protects against age-related diseases. However, many people are unable to perform an endurance exercise regimen due to illness, disability, advanced age or a work schedule that enforces sedentary behavior. Furthermore, humans have wide individual differences in their response to exercise. The genetic factors that cause this variance are not well understood. Here, we propose to use the fruit fly genetic model system to identify the causes of this variance. In the process, we will identify novel targets for therapeutic pharmaceuticals that can mimic the benefits of exercise in patients that are unable to complete an exercise program. Preliminary data strongly shows that activation of octopaminergic neurons during exercise is critical for inducing metabolic adaptations in muscle and fat. Furthermore, treatment with octopamine is capable of inducing exercise adaptations in sedentary flies. Here, we will identify which receptor or receptors are required for octopamine signaling to induce these benefits (Aim 1). Secondly, we will take advantage of sex-specific differences in exercise response in flies to identify the genetic differences that cause individual variation in response to daily exercise. These results will 1) inform the development of diagnostics to predict individual responses to exercise training, and 2) provide novel targets for therapeutics to provide the benefits of exercise to sedentary patients.