The role of the amygdala in weight gain susceptibility

描述（由申请人提供）：环境因素有能力促进其他健康个体的暴饮暴食和体重增加，因此有助于肥胖的发展。重要的是，即使在代谢过程没有任何缺陷的情况下，在环境因素的影响下也可能发生暴饮暴食。在这些因素中，与食物供应相关的外部线索刺激和维持食物摄入独立于营养状态的任何缺陷。虽然动物模型的研究已经确定杏仁核复合体是影响食物相关线索对食物摄入影响的一个基本大脑区域，但对于人类的哪些脑回路支持这种机制，我们知之甚少。本研究的总体目标是采用行为和功能神经成像方法来测试环境和代谢如何影响杏仁核-下丘脑回路的加工并促进暴饮暴食的新模型。在一系列的研究中，我们将测试人类杏仁核是否介导食物相关线索对食物摄入和体重的影响。我们的功能性神经成像数据将允许我们确定这些杏仁核对食物线索的反应的大小是否是长期（例如12个月）体重增加的可靠预测指标。该项目的具体目的如下：(1)确定超重/肥胖受试者饱腹后杏仁核对食物刺激的反应变化是否会改变，以及这种异常反应是否可以作为体重增加易感性的预测因子；(2)确定急性应激时杏仁核对食物的反应是否改变，如果改变，超重/肥胖受试者的这种反应是否增强，从而预测体重增加的易感性；(3)确定超重/肥胖受试者的杏仁核对与热值相关的香味和风味的反应是否发生了变化，这些变化是否与代谢因素有关，以及对热量修复的风味线索的异常反应是否可以作为体重增加易感性的预测因子。我们的一般假设是，一个人对食物线索的杏仁核反应的大小可以定量预测12个月内体重增加的易感性。与这一假设一致，我们的初步数据表明，超重个体的杏仁核对食物线索的反应增强，这种反应的强度是体重增加的可靠预测指标。这些研究将进一步加深我们对环境因素对人类食物摄入和体重影响的大脑机制的理解，特别是提出人类杏仁核神经对环境因素的反应是长时间内体重增加易感性的定量预测因子。

DESCRIPTION (provided by applicant): Environmental factors have the ability to facilitate overeating and weight gain in otherwise healthy individuals, and therefore contribute to the development of obesity. Importantly, overeating under the influence of environmental factors might occur even in the absence of any deficiencies in metabolic processes. Among such factors, external cues associated with food availability stimulate and sustain food intake independently of any deficits in nutritional state. While research with animal models has established the amygdalar complex as a brain region fundamental for the influence of food-associated cues on food intake, much less is known about which brain circuits support such mechanisms in humans. The overall aim of this proposal is to employ behavioral and functional neuroimaging methods to test a novel model of how the environment and metabolism influence processing in the amygdala-hypothalamic circuit and promote overeating. In a series of studies we will test whether the human amygdala mediates the influence of food-associated cues on food intake and body weight. Our functional neuroimaging data will allow us to determine whether the magnitude of these amygdale responses to food cues is a reliable predictor of longer-term (e.g., twelve months) weight gain. The specific aims of the proposed project are as follows: (1) To determine whether changes in amygdala responses to food stimuli following satiation are altered in overweight/obese human subjects, and whether such abnormal responses function as predictors of weight gain susceptibility; (2) to determine whether amygdala responses to foods are altered during acute stress, and if so, whether this response is enhanced in overweight/obese subjects and thus predicts weight gain susceptibility; and (3) to determine whether changes in amygdale responses to aromas and flavors associated with caloric value are altered in overweight/obese subjects, whether these changes are associated with metabolic factors, and whether abnormal responses to caloriepaired flavor cues function as predictors of weight gain susceptibility. Our general hypothesis states that the magnitude of amygdala responses to food cues in an individual yields quantitative predictions on weight gain susceptibility over a period of 12 months. Consistent with this hypothesis, our preliminary data shows that amygdala response to food cues is enhanced in overweight individuals and that the magnitude of such response is a reliable predictor of weight gain. The proposed studies will further our understanding of the brain mechanisms mediating the influence of environmental factors on food intake and body weight in humans, and in particular proposes human amygdala neural responses to environmental factors as a quantitative predictor of weight gain susceptibility over extended periods of time.