Neurobehavioral correlates of individual differences in obesity susceptibility

项目摘要 肥胖是一个主要的公共卫生问题，需要有效的治疗。的发展。 个性化和有效的肥胖治疗将受益于对个体差异的调查 潜在的肥胖易感性。在人类中，预测者关注的是基于特征的认知因素，但 在动物身上的研究可以评估神经、激素、行为和能量机制，这些机制不可能是 在人类身上进行了评估。胃肠道(GI)饱足对食物摄取抑制效应的敏感性变化 信号是导致这些个体差异的因素之一。我们新奇的初步数据显示 降低对胆囊素(CCK)摄取抑制作用的行为敏感性，CCK是这些GI信号之一， 预测高脂饮食(HFD)导致的体重(BW)增加。此外，行为能力下降的大鼠 CCK表达对食物摄取抑制效应的敏感性降低了后脑的Fos免疫反应 孤束核(NTS)负责处理GI发出的迷走神经传递信号。另一个预测因素是 肥胖是体重的短期自然变化。新的初步工作表明，更大的日常变化 体重预测高脂饮食诱导的总体重增加。基于令人振奋的初步发现，这项提案的总体目标 是为了研究这两个肥胖预测因素背后的生理机制。这些建议的目标 将检验这样一种假设，即神经、行为和能量平衡调节的个体差异 导致肥胖的机制不同。具体地说，我们将调查迷走的- 介导的传入性饱足信号传递给个体对摄入抑制行为敏感性的差异 CCK和随后HFD诱导的体重增加的影响(目标1)，表征NTS神经元激活的作用 在CCK敏感性和体重增加方面的个体差异(目标2)，并定义行为和精力 导致体重增加的短期体重变化的潜在机制(目标3)。团结在一起， 建议的目标将强调这些易感性预测因素背后的生理机制和 高脂饮食所致肥胖的个体差异。

Project Summary Obesity is a major public health concern for which effective treatments are needed. The development of personalized and effective obesity treatment would benefit from an investigation into the individual differences underlying obesity susceptibility. In humans, predictors have focused on trait-based cognitive factors, but basic research in animals can evaluate the neural, hormonal, behavioral and energetic mechanisms that can’t be evaluated in humans. Variation in sensitivity to the food intake inhibitory effects of gastrointestinal (GI) satiation signals is one such factor contributing to these individual differences. Our novel preliminary data show that reduced behavioral sensitivity to the intake inhibitory effects of cholecystokinin (CCK), one of these GI signals, predicts greater high fat diet (HFD)-induced body weight (BW) gain. Additionally, rats with reduced behavioral sensitivity to the food intake inhibitory effects of CCK express reduced Fos immunoreactivity in the hindbrain nucleus tractus solitarius (NTS), that processes GI derived vagally communicated signals. Another predictor of obesity is short-term natural variation in BW. Novel preliminary work shows that greater day-to-day variation in BW predicts total HFD-induced BW gain. Based on exciting preliminary findings, the overall goal of this proposal is to investigate the physiological mechanisms underlying these two predictors of obesity. These proposed aims will test the hypothesis that individual differences in neural, behavioral and energetic energy balance regulatory mechanisms differentially predispose obesity. Specifically, we will investigate the contribution of vagally- mediated afferent satiation signaling to individual differences in behavioral sensitivity to the intake suppressive effects of CCK and subsequent HFD-induced BW gain (Aim 1), characterize the role of NTS neuronal activation in individual differences in CCK sensitivity and BW gain (Aim 2) and define the behavioral and energetic mechanisms underlying short-term BW variability that leads to increased BW gain (Aim 3). Together, the proposed aims will highlight the physiological mechanisms underlying these predictors of the susceptibility and individual differences in HFD-induced obesity.