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

项目摘要 袖状胃切除术（SG）和Roux-en-Y胃旁路术（RYGB）是最有效的减肥方法 严重肥胖症的治疗方法我们的实验室最近发现，大脑对高能量的奖励激活减少 在SG和RYGB两者之后，比较高密度（HED）与低能量密度（LED）食物线索。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 最近关于酒精摄入量增加和2年内新发酒精使用障碍（AUD）的证据 手术后尽管在食物摄入和酒精使用的基础上存在重叠的神经奖励通路， 手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中的酒精吸收更快，这可能是酒精摄入量增加的一个因素。 然而，还没有研究过术后一段时间内酒精的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70人进行研究： SG、RYGB和非治疗（NT）组，在基线BMI、性别、年龄和酒精摄入量方面匹配， 术前、1年（体重趋于稳定时）和术后2年（酒精摄入量增加时）。 虽然SG和RYGB的体重减轻相似，但手术解剖结构不同，但导致相似的 增加了饮酒量，这两种情况都值得研究。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食品的视觉线索。从事前到事后 手术后，9种常见奖励ROI对酒精和食物的提示反应预计会增加， ALC与NA的提示，并减少到HED与LED。预计这些变化将在1年后显现， 术后2年。B）将对ALC与NA线索的神经反应的变化与酒精摄入量的变化相关联，# 1年和2年时的AUD症状和AUD状态。c）测试是否基线奖励激活ALC与NA线索 预测术后1年和2年的酒精摄入量增加。d）对于上述，比较（SG + RYGB）与NT（主要）和RYGB与SG（次要），预计RYGB的影响大于SG。 主要目的2：a）测定血液中酒精含量相当于1杯酒精饮料后的药代动力学（PK） 在饮用前、饮用后2、5、15、25、35、50、65、80分钟时的血液中的BAC浓度（BAC）。我们希望手术 RYGB组的BAC峰值比NT组高且早，RYGB组的BAC峰值比NT组高且早 BAC比SG。B）将大脑激活的变化与共同奖励区域中的ALC与NA线索相关联， 根据BAC峰值和峰值时间的变化预测酒精摄入量和AUD 时间到了。研究结果应加强对手术后神经机制的认识。 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 开发新的外科手术程序，不会导致酒精摄入量增加。

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.