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; 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.

项目摘要 套筒胃切除术（SG）和roux-en-y胃旁路（RYGB）是最有效的体重（WT）损失 严重肥胖的程序。我们的实验室最近显示出对高能量的大脑奖励激活减少 SG和RYGB之后，致密（HED）与低能密集（LED）食品提示。奖励激活 但是，变化与HED或LED食物的实际摄入量的变化没有相关。也有 关于酒精摄入量增加和新发作酒精使用障碍（AUD）的最新证据 术后。尽管食物摄入和饮酒的基础神经奖励途径重叠，但 增加酒精摄入术后手术的机制尚不清楚。但是，有证据表明 SG和RYGB的酒精吸收更快，这可能是酒精摄入量增加的一个因素。 然而，随着时间的流逝，尚未对酒精吸收进行研究，以将其与酒精摄入量增加有关 或aud。为了研究神经生物学机制，我们将对三组70组进行研究： SG，RYGB和一个非治疗（NT）组，在基线BMI，性别，年龄和酒精摄入量匹配， 预科，1 y（体重趋于稳定时）和2年的外科手术（当酒精摄入量增加时）。 尽管SG和RYGB的体重减轻相似，但手术在解剖学上有所不同，但导致相似 饮酒增加，使它们都值得学习。主要目的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。从帖子到职位 手术，提示反应性在9个常见的奖励中对酒精和食物的反应性有望增加 ALC与Na的提示，并减少到HED与LED。预计变化将在1 y处体现并加强 术后2年。 b）将神经反应与ALC与NA线索的变化与酒精摄入的变化相关联，＃ AUD症状和1和2 y的AUD状态。 c）测试基线奖励是否激活ALC与NA提示 预测在1和2 y时外科酒精摄入量增加。 d）比较上述内容（sg + RYGB）与NT（主要）和RYGB vs SG（次要），对RYGB的影响比SG更大。 主要目的2：a）从血液酒精等同的酒精饮料后确定药代动力学（PK） 饮食前2、5、15、25、35、50、65、80分钟，浓度（BAC）。我们期望手术 小组将比NT表现出更高和更快的BAC峰，并且RYGB将导致更高和更早的峰 BAC比SG。 b）将大脑激活的变化与公共奖励领域中的ALC与NA提示相关联 基于BAC峰值的变化，BAC峰值和峰值酒精摄入量和AUD的时间变化 是时候达到顶峰。研究结果应增强术后神经机制的知识 酒精和食物摄入的变化与酒精PK的变化有关。这些知识可能导致 开发新的手术程序不会导致酒精摄入量增加。