How does the brain stop us overeating? Neuro-genetic control of eating, and how it changes with age.

大脑如何阻止我们暴饮暴食？

• 批准号: 2873201
• 金额: --
• 依托单位: University of Kent
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2873201
• 关键词: How; does; brain; stop; us

Obesity and age are major risk factors for a range of serious health complications. By understanding the intricate connections between our environment, genetics, nervous system, and body at different life stages, we can find ways to improve our health, and where necessary treat disease. Many genes linked to obesity are implicated in the neuronal signalling pathways that control eating behaviours. Appetite drives food consumption and satiety is the feeling of fulness after eating, to stop further food intake. Information on food is obtained via the sensory nervous system and integrates with internal cues from the body relating to hunger or satiety. These signals control food intake, maintain homeostasis and prevent disease. Our lab has identified a new genetic component of this system in C. elegans, and hypothesise that it acts in a neuronal-physiological-behavioural axis to influence eating behaviour and metabolism across species. This gene (SKN-1/Nrf) acts in neurons to receive signals from the environment, integrate them and harness hormonal and neuromodulator signalling connections to alter the animals behaviour and muscle/mitochondrial physiology (Tataridas-Pallas et al., 2021 PLoS Genetics). Our eating habits also change dramatically with age, as does our metabolism and body composition. SKN-1/Nrf is also a well-characterised longevity gene (Tullet et al, 2008 Cell, Tullet et al., 2017 Aging Cell), and as food intake has massive implications for age-related diseases (e.g. diabetes, cancer, cardiovascular disease) which are also impacted by over eating, by studying SKN-1's neurological role we will be able to link eating behaviours, longevity, and age-related health so that they can be harnessed to improve the health and fitness of our population. The mammalian equivalent of SKN-1, Nrf, is also expressed in the brain important for regulating eating behaviour (hypothalamus), suggesting a new, as yet uncovered role for this gene in humans. This creative, curiosity-driven project will provide a step change in the way we view Nrf function. We are offering a multi-disciplinary project will use the pioneering whole organism system C. elegans to study SKN-1 neurobiology (Tullet lab), and mammalian cell culture to study Nrf (Fenton lab). Using genetics, molecular and cellular biology, and a variety of physiological, metabolic and behavioural assays you will map the neurotransmitters and neuropeptide circuits involved in eating behaviour, discover the transcriptional role of SKN-1/Nrf, and fully explore the physiological effects of disrupted eating behaviours on the mitochondria and whole body physiology across the life course.

肥胖和年龄是一系列严重健康并发症的主要风险因素。通过了解我们的环境，遗传学，神经系统和身体在不同生命阶段之间的复杂联系，我们可以找到改善健康的方法，并在必要时治疗疾病。许多与肥胖有关的基因都与控制饮食行为的神经信号通路有关。食欲驱动食物消耗，饱腹感是进食后的饱腹感，以停止进一步的食物摄入。关于食物的信息是通过感觉神经系统获得的，并与来自身体的与饥饿或饱腹感有关的内部线索相结合。这些信号控制食物摄入，维持体内平衡并预防疾病。我们的实验室已经在C. elegans，并假设它在神经元-生理-行为轴中起作用，以影响跨物种的饮食行为和代谢。该基因（SKN-1/Nrf）在神经元中起作用以接收来自环境的信号，整合它们并利用激素和神经调节剂信号传导连接来改变动物行为和肌肉/线粒体生理学（Tataridas-Pallas et al. 2021 PLoS Genetics）。我们的饮食习惯也随着年龄的增长而发生巨大变化，我们的新陈代谢和身体成分也是如此。SKN-1/Nrf也是一种充分表征的长寿基因（Tullet et al.，2008 Cell，Tullet et al.，2017年衰老细胞），食物摄入量对与年龄相关的疾病（如糖尿病，癌症，心血管疾病）有着巨大的影响，这些疾病也受到过度饮食的影响，通过研究SKN-1的神经作用，我们将能够将饮食行为，长寿和与年龄相关的健康联系起来，以便利用它们来改善我们人口的健康和健身。SKN-1的哺乳动物等价物Nrf也在大脑中表达，对调节饮食行为（下丘脑）很重要，这表明该基因在人类中有一个新的尚未发现的作用。这个创造性的，好奇心驱动的项目将为我们看待Nrf功能的方式提供一个步骤。我们正在提供一个多学科的项目将使用开创性的整个生物系统C。线虫研究SKN-1神经生物学（Tullet实验室），哺乳动物细胞培养研究Nrf（芬顿实验室）。利用遗传学，分子和细胞生物学以及各种生理，代谢和行为分析，您将绘制参与饮食行为的神经递质和神经肽回路，发现SKN-1/Nrf的转录作用，并充分探索破坏饮食行为对线粒体和整个生命过程中的全身生理学的生理影响。