Relation of individual differences in fMRI-Assessed Satiation Signaling to Obesity Risk and Future Weight Gain

功能磁共振成像评估的饱腹感信号个体差异与肥胖风险和未来体重增加的关​​系

• 批准号: 10658292
• 负责人: Kyle S. Burger
• 金额: $ 63.55万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-15 至 2028-05-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10658292
• 关键词: Adipose tissue; Adolescence; Adolescent; Affect; Appetite Depressants; Attenuated; Behavioral; Body Composition; Body Weight decreased; Body fat; Body measure procedure; Brain; Brain region; Calories; Cerebrovascular Disorders; Cognitive; Consumption; Corpus striatum structure; Cues; Data; Dementia; Disease; Eating; Energy Intake; Fasting; Fingerprint; Food; Functional Magnetic Resonance Imaging; Future; Habits; Hormones; Hyperphagia; Impaired cognition; Individual; Individual Differences; Knowledge; Malignant Neoplasms; Measures; Metabolic Diseases; Modeling; Myocardial Infarction; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Participant; Pattern; Peptides; Perception; Persons; Premature Mortality; Prevention program; Process; Prospective Studies; Regulation; Reporting; Research; Research Design; Rewards; Risk; Satiation; Scanning; Signal Transduction; Structure; Structure of postcentral gyrus; Taste Perception; Testing; Thinness; Visceral fat; Weight Gain; Youth; adult obesity; aged; connectome; design; excessive weight gain; follow-up; glucagon-like peptide 1; healthy weight; high risk; improved; indexing; maternal obesity; multimodality; neural; neurobehavioral; novel; obesity risk; obesity treatment; recruit; response; weight loss program

SUMMARY Obesity affects 2.8 billion people worldwide and is the second leading cause of premature mortality. Unfortunately, current treatments do not produce lasting weight loss, potentially because of an incomplete understanding of the risk processes that promote obesity. After eating to fullness individuals with obesity versus without obesity show weaker satiation signaling, as indexed by elevated responsivity of reward valuation and gustatory regions in response to food cues and food tastes and stronger connectivity between these brain regions. Behaviorally, obesity is associated with consumption of excess calories ab libitum when sated, along with reduced perceived fullness and less perception of homeostatic signals during satiation. Although research has established that obesity is correlated with weaker satiation signaling, no study has determined whether weaker satiation signaling increases the risk for future overeating and weight gain or is a consequence of overeating. Thus, we propose to conduct a rigorous prospective study designed to determine the direction of influence between these two variables. We will recruit 132 healthy-weight adolescents (aged: 13-16; n=80 at high risk for obesity virtue of maternal obesity) for a multimodal, repeated-measures study using a novel fMRI paradigm designed to capture neurobehavioral changes over the course of eating to satiation. We will also include objective measures of body fat, food intake, gut hormones, and cognitive measures. Aim 1: We will a) test the hypothesis that over the course of eating to satiation healthy-weight adolescents at high-risk versus low-risk for obesity (virtue of maternal obesity) will show persistently elevated brain response to energy-dense food tastes in the striatum, postcentral gyrus, and gustatory cortex. Aim 2: We will a) test the hypothesis that participants who show weaker satiation signaling, as evidenced by persistently elevated responsivity in the striatum, postcentral gyrus, and gustatory regions after eating to fullness will show elevated future body fat gain over a 3-year follow-up, and b) test the ability of individual differences in a satiated brain fingerprint to predict future body fat gain over a 3-year follow-up. Aim 3: Test the hypothesis that the degree of percent body fat gain at 3-year follow-up will be related to a reduction in satiation signaling, as indexed by a) higher responsivity in striatal, postcentral gyrus, and gustatory regions after eating to fullness over the course of satiation, and b) increased engagement of these regions in a brain fingerprint when satiated. If data provide support for Aims 1 and 2, but not Aim 3, results would suggest that weaker satiation signaling increases risk for weight gain. In contrast, if data provide support for Aim 3, but not Aim 1 and 2, results would suggest that weaker satiation signaling is a consequence of overeating. Finally, if data provide support for all 3 Aims, results would suggest that weaker satiation signaling increases risk for overeating and weight gain, and further that this overeating further attenuates satiation signaling in a dynamic feed-forward fashion.

概括 肥胖影响着全世界 28 亿人，是过早死亡的第二大原因。 不幸的是，目前的治疗方法并不能产生持久的减肥效果，可能是因为不完全的原因 了解促进肥胖的风险过程。肥胖者吃饱后 与没有肥胖的人相比，饱腹感信号较弱，如奖励反应性升高所表明的 评估和味觉区域响应食物线索和食物口味以及之间更强的连通性 这些大脑区域。从行为上来说，肥胖与任意摄入过量热量有关： 饱腹感，以及饱腹感的减少和饱足期间稳态信号的感知减少。 尽管研究已经证实肥胖与较弱的饱足感信号相关，但尚无研究表明 确定较弱的饱足感信号是否会增加未来暴饮暴食和体重增加的风险，或者是 暴饮暴食的后果。因此，我们建议进行一项严格的前瞻性研究，旨在确定 这两个变量之间的影响方向。我们将招募132名健康体重的青少年（年龄： 13-16；一项多模式、重复测量研究中，n = 80 名因母亲肥胖而处于肥胖高风险的人 使用一种新颖的功能磁共振成像范例来捕捉饮食过程中的神经行为变化 饱腹感。我们还将包括身体脂肪、食物摄入量、肠道激素和认知能力的客观测量 措施。目标 1：我们将 a) 检验以下假设：在进食至饱腹感的过程中，体重达到健康水平 肥胖高风险青少年与肥胖低风险青少年（母亲肥胖的优点）将表现出持续升高 大脑纹状体、中央后回和味觉皮层对高能量食物味道的反应。目标2：我们 a) 测试以下假设：表现出较弱饱足感信号的参与者，如持续存在所证明 吃饱后纹状体、中央后回和味觉区的反应性升高 在 3 年的随访中增加未来的体脂增加，并且 b) 测试个体差异的能力 饱腹感的大脑指纹可预测三年随访期间未来的身体脂肪增加。目标 3：检验假设 三年随访时体脂百分比增加的程度将与饱足感信号的减少有关，因为 a) 吃饱后纹状体、中央后回和味觉区的反应性更高 在饱腹感的过程中，b）饱腹感时这些区域在大脑指纹中的参与度增加。 如果数据支持目标 1 和 2，但不支持目标 3，则结果表明饱足感信号较弱 增加体重增加的风险。相反，如果数据支持目标 3，但不支持目标 1 和 2，则结果将 表明饱腹感信号较弱是暴饮暴食的结果。最后，如果数据支持所有 3 个 目标，结果表明，较弱的饱腹感信号会增加暴饮暴食和体重增加的风险，并且 此外，这种暴饮暴食会以动态前馈方式进一步减弱饱足感信号。