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

总结 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，这可能是因为不完全的 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，表现出较弱的饱足信号，这是由奖励的反应性升高所指示的。 评价和味觉区域对食物线索和食物味道的反应， 这些大脑区域。从行为上讲，肥胖与随意摄入过量卡路里有关， 饱足，沿着减少的饱足感和饱足期间较少的稳态信号感知。 虽然研究已经证实肥胖与较弱的饱足信号有关，但没有研究表明， 确定较弱的饱足信号是否会增加未来暴饮暴食和体重增加的风险， 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，以确定 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; n=80，由于母亲肥胖而具有肥胖高风险）进行多模式重复测量研究 使用一种新的功能磁共振成像模式，旨在捕捉进食过程中的神经行为变化， 饱食我们还将包括身体脂肪，食物摄入量，肠道激素和认知的客观措施 措施目的1：我们将a）检验假设，即在吃饱的过程中， 处于肥胖高风险与低风险（由于母亲肥胖）的青少年将显示持续升高的 大脑对纹状体、中央后回和味觉皮层中高能量食物味道的反应。目标2：我们 将a）测试以下假设，即表现出较弱的饱足信号的参与者，如持续的饱足信号所证明的， 在吃到饱后，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，和B）测试个体差异的能力， 饱足的大脑指纹，以预测未来的身体脂肪增加超过3年的后续行动。目标3：检验假设， 3年随访时体脂增加百分比的程度与饱食信号的减少有关， 指数为a）进食至饱后，纹状体、中央后回和味觉区的反应性更高 以及B）当饱足时，这些区域在大脑指纹中的参与增加。 如果数据支持目标1和目标2，但不支持目标3，则结果将表明较弱的饱足信号 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和目标2，则结果将 表明较弱的饱足信号是暴饮暴食的结果。最后，如果数据支持所有3个 结果表明，较弱的饱足信号增加了暴饮暴食和体重增加的风险， 此外，这种过度进食进一步以动态前馈方式衰减饱足信号。

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.