Neuroimaging to investigate mechanisms underlying changes in Intake of high energy dense foods and alcohol from pre to post bariatric surgery

神经影像学研究减肥手术前后高能量密度食物和酒精摄入量变化的机制

• 批准号: 10639188
• 负责人: ALLAN GELIEBTER
• 金额: $ 60.29万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-05 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10639188
• 关键词: Address; Age; Alcohol consumption; Alcohols; Amygdaloid structure; Anatomy; Anterior; Area; Back; Blood alcohol level measurement; Body Weight; Body Weight decreased; Body mass index; Brain; Calories; Clinical; Clinical Trials; Cues; Development; Drug Kinetics; Eating; Enrollment; Exhibits; Food; Frontal gyrus; Functional Magnetic Resonance Imaging; Gas Chromatography; Gastrectomy; Gastric Bypass; Incidence; Inferior frontal gyrus; Insula of Reil; Intake; Interview; Knowledge; Lead; Link; Matched Group; Measures; Medial; Modeling; Morbid Obesity; Neurobiology; Operative Surgical Procedures; Outcome Measure; Pathway interactions; Precentral gyrus; Procedures; Research; Rewards; Risk; Source; Symptoms; Testing; Time; Venous blood sampling; Ventral Striatum; Visual; absorption; alcohol cue; alcohol response; alcohol use disorder; bariatric surgery; cingulate cortex; comorbidity; cue reactivity; drinking; effective therapy; neural; neurobiological mechanism; neuroimaging; neuromechanism; new therapeutic target; prevent; primary outcome; response; sex; timeline

PROJECT SUMMARY Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the most effective weight (wt) loss procedures for severe obesity. Our lab recently showed decreased brain reward activation to high energy dense (HED) vs low energy dense (LED) food cues following both SG and RYGB. The reward activation changes, however, have not been correlated with changes in actual intake of HED or LED foods. There is also recent concerning evidence of increased alcohol intake and new onset alcohol use disorder (AUD) by 2 y postsurgery. Although there are overlapping neural reward pathways underlying food intake and alcohol use, the mechanisms behind increased alcohol intake postsurgery remain unknown. There is, however, evidence of more rapid alcohol absorption in both SG and RYGB, which could be a factor in increased alcohol intake. Alcohol absorption, however, has not been studied over time postsurgery to link it to increased alcohol intake or AUD. To investigate the neurobiological mechanisms, we will conduct a study of three groups of 70 each: SG, RYGB, and a nontreatment (NT) group, matched for baseline BMI, sex, age, and alcohol intake, at presurgery, 1 y (when body weight tends to stabilize), and 2 y postsurgery (when alcohol intake increases). Although weight loss is similar for SG and RYGB, the surgeries differ anatomically, yet lead to similar increased drinking, making them both worthwhile to study. Primary Aim 1: a) Determine neural responses to visual cues of alcohol (ALC) and non-alcohol (NA) drinks as well as HED and LED foods. From pre to post surgery, cue reactivity in 9 common reward ROIs to alcohol and food is expected to increase in response to cues of ALC vs NA and decrease to HED vs LED. The changes are expected to manifest at 1 y and strengthen at 2 y postsurgery. b) Relate changes in neural responses to ALC vs NA cues with changes in alcohol intake, # AUD symptoms, and AUD status at 1 and 2 y. c) Test whether baseline reward activation to ALC vs NA cues predicts increased postsurgical alcohol intake at 1 and 2 y. d) Compare for the above, the effects of (SG + RYGB) vs NT (primary) and RYGB vs SG (secondary), expecting greater effects for RYGB than SG. Primary Aim 2: a) Determine pharmacokinetics (PK) after 1 alcohol drink equivalent from blood alcohol concentrations (BAC) at pre-drink, 2, 5, 15, 25, 35, 50, 65, 80 min post-drink. We expect that the surgical groups will exhibit higher and sooner BAC peaks than NT, and that RYGB will result in higher and earlier peak BAC than SG. b) Correlate changes in brain activation to ALC vs. NA cues in the common reward areas with changes in BAC peak and time to peakpredict alcohol intake and AUD based on changes in BAC peak and time to peak. The study results should enhance knowledge of neural mechanisms underlying the postsurgical changes in alcohol and food intake, in association with changes in alcohol PK. This knowledge could lead to development of new surgery procedures which do not lead to increased alcohol intake.

项目概要 袖状胃切除术 (SG) 和 Roux-en-Y 胃绕道手术 (RYGB) 是最有效的减肥 (wt) 方法 严重肥胖的手术。我们的实验室最近显示，大脑对高能量的奖励激活减少 遵循 SG 和 RYGB 的高能量密度 (HED) 与低能量密度 (LED) 食物提示。奖励激活 然而，这些变化与 HED 或 LED 食品实际摄入量的变化无关。还有 最近有关酒精摄入量增加和新发酒精使用障碍 (AUD) 2 年的证据 术后。尽管食物摄入和饮酒之间存在重叠的神经奖励通路， 术后酒精摄入量增加的机制仍不清楚。然而，有证据表明 SG 和 RYGB 的酒精吸收速度更快，这可能是酒精摄入量增加的一个因素。 然而，尚未研究术后一段时间内酒精吸收与酒精摄入量增加的关系 或澳元。为了研究神经生物学机制，我们将对三组进行研究，每组 70 人： SG、RYGB 和非治疗 (NT) 组，匹配基线 BMI、性别、年龄和酒精摄入量， 术前、1 年（体重趋于稳定时）和术后 2 年（酒精摄入量增加时）。 尽管 SG 和 RYGB 的减肥效果相似，但手术在解剖学上有所不同，但结果却相似 饮酒量增加，使他们都值得研究。主要目标 1：a) 确定神经反应 酒精 (ALC) 和非酒精 (NA) 饮料以及 HED 和 LED 食品的视觉提示。从前到后 手术后，9种常见奖励投资回报率对酒精和食物的提示反应预计会随着手术而增加 ALC 与 NA 的对比，并减少到 HED 与 LED 的对比。这些变化预计将在一年内显现并加强 术后 2 年。 b) 将 ALC 与 NA 线索的神经反应变化与酒精摄入量的变化联系起来，# AUD 症状以及 1 岁和 2 岁时的 AUD 状态。 c) 测试 ALC 与 NA 线索的基线奖励激活是否相同 预测术后 1 年和 2 年酒精摄入量增加。 d) 比较以上，(SG + RYGB）与 NT（主要）以及 RYGB 与 SG（次要）相比，预计 RYGB 的效果比 SG 更大。 主要目标 2：a) 从血液酒精中确定 1 杯酒精当量后的药代动力学 (PK) 饮酒前、饮酒后 2、5、15、25、35、50、65、80 分钟的浓度 (BAC)。我们预计手术 组将表现出比 NT 更高和更早的 BAC 峰值，并且 RYGB 将导致更高和更早的峰值 BAC 高于 SG。 b) 将大脑激活的变化与常见奖励区域中的 ALC 与 NA 线索相关联 BAC 峰值和达到峰值时间的变化根据 BAC 峰值和达到峰值时间的变化预测酒精摄入量和 AUD 达到高峰的时间。研究结果应增强对术后神经机制的了解 酒精和食物摄入量的变化与酒精 PK 的变化相关。这些知识可能会导致 开发不会导致酒精摄入量增加的新手术程序。