Metabolic signatures and neurophysiological mechanisms of bad food decisions.

脊椎动物和无脊椎动物必须应对食物供应的变化，以保持正能量平衡。良好的能量平衡对个人健康是不可或缺的。能量密集食物摄入的增加或缺乏运动的增加是肥胖和超重的根本原因。另一方面，饥饿或营养不良引起热量摄入不足引起的痛苦感觉，导致广泛的生理变化，直至器官损伤和死亡。在某种程度上，进行性营养不良会引起个人不可避免地决定摄入通常避免的劣质食物。我们的项目旨在了解脑-体通讯发生了什么样的变化，从而导致摄入通常避免的劣质食物。我们的目标是确定代谢特征和触发不良食物决定的神经生理机制。有趣的是，我们假设潜在的变化也发生在肥胖中，这是营养不良的另一个极端。因此，我们的目标是在代谢、神经生理和内分泌水平上对不良喂养决定有一个全面的了解。该项目将利用果蝇的实验潜力来研究不良食物决策的代谢和神经生理基础。我们将把多组学策略（代谢组学、转录组学和蛋白质组学）与神经遗传学（如光遗传学）、行为研究、高分辨率显微镜和活细胞成像（Ca2+和FRET成像）结合起来，并相信这种科学方法将为不良食物决策的机制提供新的见解。针对饥饿驱动的饮食行为（包括不良食物决定）的潜在机制，可能有助于通过提高患者对减肥干预措施的依从性来推进治疗策略。

Vertebrate and invertebrate species have to deal with changes in food availability in order to keep a positive energy balance. A well-balanced energy homeostasis is indispensable for the individual´s health. An increased intake of energy-dense food or an increase in physical inactivity are fundamental causes of obesity and overweight. On the other side hunger or malnutrition induces painful sensation caused by insufficient caloric intake leading to extensive physiological changes up to organ damage and death. At a certain point, progressive malnutrition evokes the individual´s inevitable decision to intake food of bad quality which is normally avoided. Our project aims to understand what kind of changes occur in brain-body communication to induce the intake of bad quality food, that is normally avoided. We aim to identify the metabolic signatures and neurophysiological mechanisms that triggers bad food decisions. Interestingly, we assume that the underlying changes also occur in obesity, the other extreme of malnutrition. Therefore, we aim a holistic understanding of bad feeding decisions on a metabolic, neurophysiological, and endocrinological level. The project will exploit the experimental potential of Drosophila to study the metabolic and neurophysiological basis of bad food decisions. We will combine a multiomics strategy (metabolomics, transcriptomics and proteomics) with neurogenetics (e.g. optogenetics), behavioral studies, high resolution microscopy and live cell imaging (Ca2+ and FRET imaging) and are convinced that this scientific approach will provide new insights into the mechanisms of bad food decisions. Targeting mechanisms underlying hunger-driven eating behavior including bad food decisions may help to advance therapeutic strategies by improving patients´ compliance to body weight loss interventions.