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An fMRI Test of the Dynamic Vulnerability Model of Obesity: Risk Factor Plasticit

肥胖动态脆弱性模型的功能磁共振成像测试：可塑性风险因素

基本信息

批准号：
9061670
负责人：
ERIC M STICE
金额：
$ 45.86万
依托单位：
OREGON RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-15 至 2018-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9061670
关键词：
16 year old Address Adolescent Alleles Behavioral Body fat Brain imaging Cessation of life Corpus striatum structure Coupled Cues Data Data Analytics Dopamine Dopamine D2 Receptor Dopamine Receptor Down-Regulation Eating Fatty acid glycerol esters Food Functional Magnetic Resonance Imaging Functional disorder Future Genetic Risk Growth Healthcare Human Hyperphagia Image Incentives Intake Intervention Lead Literature Measures Modeling Neuronal Plasticity Obesity Oral Preventive treatment Process Public Health Rattus Rewards Risk Risk Factors Scanning Signal Transduction Stimulus Techniques Teenagers Testing Thinking Weight Gain Youth base behavioral response clinical practice conditioning design discounting dopaminergic neuron feeding follow-up improved novel obesity risk predicting response prevent prospective receptor density response reward circuitry somatosensory sugar

项目摘要

DESCRIPTION (provided by applicant): Obese vs lean humans show greater gustatory/oral somatosensory and reward region responsivity to palatable food images/cues and this predicts future weight gain (Yokum et al., in press; Prelim Studies; Stice et al., 2008a,d, 2010b; Stoeckel et al., 2008), in line with reward surfeit and incentive sensitization models of obesity (Berridge, 2009; Davis et al., 2004). Yet, obese vs lean humans have fewer dopamine (DA) receptors in striatal reward regions, show reduced striatal response to palatable food intake, and low striatal response predicts future weight gain in those at genetic risk for reduced DA signaling (Felsted et al., 2010; Stice et al., 2008a,d; Wang et al., 2001; Volkow et al., 2008), in line with the reward deficit model of obesity (Wang et al., 2002b). One explanation for the mixed findings is that some of these findings reflect initial risk factors and others result from overeating. Firing of DA neurons in reward regions shifts from food intake to cues that predict food intake after conditioning (Kiyatkin et al., 1994; Schultz et al., 1993) and overeating leads to reduced D2 receptor density, D2 sensitivity, and reward sensitivity in rats (Alsio et al., 2010; Kelley et al. 2003; Johnson & Kenny, 2010) and striatal response to food in humans (Stice et al., 2010a), implying that overeating leads to increased incentive sensitization and down-regulation of reward regions. Further, reduced inhibitory region response to food images/cues predicts future overeating and weight gain (Cornier et al., 2010; Prelim Studies). Data imply that youth at risk for obesity initially show greater responsivity of regions that encode the reward value of food cues, coupled with greater responsivity of gustatory/oral somatosensory regions that encode the sugar and fat content of foods, and with reduced inhibitory region responsivity, which lead to overeating/weight gain that produces blunted striatal DA signaling, increased responsivity of reward valuation regions to food cues, and reduced inhibitory activation in response to food stimuli, increasing risk for further overeating/weight gain. We propose to conduct a rigorous test of this dynamic-vulnerability model using a novel repeated measures fMRI design in which teens complete scans annually over 4 years. Aim 1: test whether elevated gustatory/oral somatosensory and reward region responsivity and reduced inhibitory region responsivity to palatable food images, cues, and intake of food varying in sugar/fat content, and behavioral inhibitory control deficits/immediate reward bias predict initial increases in % body fat in 130 lean teens. Aim 2: use growth curve models to test whether initial increases in % body fat and energy dense food intake predict future decreases in striatal response to palatable food receipt, increases in reward circuitry response to palatable food images/ cues, decreased inhibitory region response to food images/cues, and increased behavioral inhibitory control deficits/immediate reward bias. Aim 3: test whether decreased striatal response to palatable food, increased reward region response to food images/cues, reduced inhibitory region response to food images/cues, behavioral inhibitory control deficits/immediate reward bias predict further escalation in % body fat.

描述（由申请人提供）：肥胖者与瘦人相比，对可口食物图像/提示表现出更大的味觉/口腔体感和奖励区域反应性，这可以预测未来的体重增加（Yokum 等人，正在出版；Prelim Studies；Stice 等人，2008a,d, 2010b；Stoeckel 等人，2008），与肥胖的奖励过度和激励敏化模型一致（贝里奇， 2009年；戴维斯等人，2004）。然而，肥胖的人与瘦的人相比，纹状体奖励区域的多巴胺 (DA) 受体较少，纹状体对可口食物摄入的反应减少，而低纹状体反应预示着那些有 DA 信号减少遗传风险的人未来的体重增加 (Felsted et al., 2010; Stice et al., 2008a,d; Wang et al., 2001; Volkow et al., 2008)，与奖励一致赤字模型肥胖（Wang 等人，2002b）。对这些混合结果的一种解释是，其中一些结果反映了最初的风险因素，而另一些则是由于暴饮暴食造成的。解雇 DA 奖赏区域的神经元在条件反射后从食物摄入转变为预测食物摄入的线索（Kiyatkin et al., 1994; Schultz et al., 1993），暴饮暴食会导致大鼠 D2 受体密度、D2 敏感性和奖赏敏感性降低（Alsio et al., 2010; Kelley et al. 2003; Johnson & Kenny, 2010）以及人类纹状体对食物的反应（Stice et al., 2010） al., 2010a)，这意味着暴饮暴食会导致激励敏感性增加和奖励区域下调。此外，抑制区域对食物图像/线索的反应减少可以预测未来的暴饮暴食和体重增加（Cornier 等人，2010；Prelim Studies）。数据表明，有肥胖风险的青少年最初表现出编码食物线索奖励值的区域的更大响应性，加上编码食物糖和脂肪含量的味觉/口腔体感区域的更大响应性，以及抑制区域响应性的降低，这导致暴饮暴食/体重增加，从而产生钝化的纹状体DA信号，奖励评估区域对食物线索的响应性增加，并减少抑制性对食物刺激的激活，增加进一步暴饮暴食/体重增加的风险。我们建议使用一种新颖的重复测量功能磁共振成像设计对这种动态脆弱性模型进行严格的测试，其中青少年在 4 年内每年完成一次扫描。目标 1：测试 130 名瘦青少年的味觉/口腔体感和奖励区响应性升高，抑制区对可口食物图像、线索和不同糖/脂肪含量的食物摄入的响应性降低，以及行为抑制控制缺陷/立即奖励偏差是否预测体脂百分比的初始增加。目标 2：使用生长曲线模型来测试身体脂肪百分比和能量密集食物摄入量的初始增加是否预示着未来纹状体对可口食物接收的反应减少，奖励电路对可口食物图像/提示的反应增加，抑制区域对食物图像/提示的反应减少，以及行为抑制控制缺陷/立即奖励偏差增加。目标 3：测试纹状体对美味食物的反应减少、奖励区域对食物图像/提示的反应增加、抑制区域对食物图像/提示的反应减少、行为抑制控制缺陷/立即奖励偏差是否预测体脂百分比进一步上升。