The role of the amygdala in weight gain susceptibility

杏仁核在体重增加易感性中的作用

• 批准号: 7789867
• 负责人: Dana M Small
• 金额: $ 77.9万
• 依托单位: JOHN B. PIERCE LABORATORY, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7789867
• 关键词: Accounting; Amygdaloid structure; Animal Experimentation; Animal Model; Behavioral; Body Weight; Brain; Brain region; Complex; Cues; Data; Development; Eating; Energy Intake; Environment; Environmental Risk Factor; Feeding behaviors; Flavoring; Food; Glucose; Hormones; Human; Hyperphagia; Hypothalamic structure; Individual; Lateral; Lead; Malnutrition; Mediating; Metabolic; Metabolism; Methods; Modeling; Monitor; Nutrient; Nutritional; Obesity; Organism; Overweight; Physiological Processes; Plasma; Plastics; Predisposition; Process; Rattus; Research; Rewards; Risk Factors; Role; Satiation; Series; Signal Transduction; Stimulus; Stress; Testing; Time; Weight Gain; acute stress; conditioning; energy balance; feeding; human subject; neuroimaging; novel; preference; public health relevance; relating to nervous system; response

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. PUBLIC HEALTH RELEVANCE: Environmental factors influence food intake and are important contributors to the development of obesity. However, the brain mechanisms underlying the influence of environmental factors on feeding in humans remain poorly understood. The overall aim of this proposal is to employ behavioral and functional neuroimaging methods to test a novel model for how the environment and metabolism influence processing in the amygdala-hypothalamic circuit to promote overeating. 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.

描述（由申请人提供）：环境因素能够促进其他健康个体的暴饮暴食和体重增加，因此导致肥胖的发生。重要的是，即使代谢过程没有任何缺陷，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，而与营养状态的任何缺陷无关。虽然对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基础大脑区域，但我们对哪些大脑回路支持人类的这种机制知之甚少。该提案的总体目标是采用行为和功能神经影像方法来测试环境和新陈代谢如何影响杏仁核-下丘脑回路的处理并促进暴饮暴食的新模型。在一系列研究中，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。我们的功能神经影像数据将使我们能够确定这些杏仁核对食物线索的反应程度是否是长期（例如十二个月）体重增加的可靠预测因素。该项目的具体目标如下：（1）确定超重/肥胖人类受试者在饱足后杏仁核对食物刺激的反应是否发生改变，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) 确定杏仁核对食物的反应在急性应激期间是否改变，如果改变，这种反应在超重/肥胖受试者中是否增强，从而预测体重增加的易感性； (3) 确定超重/肥胖受试者中杏仁核对与热量相关的香气和风味的反应是否发生改变，这些变化是否与代谢因素相关，以及对热量配对风味线索的异常反应是否可以作为体重增加的预测因素易感性。我们的一般假设表明，杏仁核对个体食物线索的反应程度可以对 12 个月内体重增加的敏感性进行定量预测。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，并且这种反应的程度是体重增加的可靠预测因素。拟议的研究将进一步加深我们对介导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对环境因素的神经反应作为长期体重增加敏感性的定量预测因子。 公共卫生相关性：环境因素影响食物摄入，是导致肥胖的重要因素。然而，环境因素影响人类进食的大脑机制仍然知之甚少。该提案的总体目标是采用行为和功能神经影像方法来测试一种新模型，以了解环境和新陈代谢如何影响杏仁核-下丘脑回路中的处理以促进暴饮暴食。拟议的研究将进一步加深我们对介导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对环境因素的神经反应作为长期体重增加敏感性的定量预测因子。