Neurobiologic Alterations in Bariatric Surgery: Taste Response and Weight Loss

描述（由申请人提供）：我是约翰霍普金斯大学医学院外科的初级教员，博士。约翰霍普金斯彭博公共卫生学院临床研究专业的候选人。我以前的工作主要集中在胃旁路术后肥胖患者脑多巴胺（DA）的变化。这个指导研究项目的目的是调查减肥手术诱导的味觉偏好的神经生物学改变，并探索味觉反应与成功的长期减肥的关系。在进行这项研究的同时，我将通过营养流行病学，神经科学和神经影像学的正式课程，并通过行为神经科学，精神病学，营养学，流行病学和手术专家团队的指导研究指导，提高我的研究知识和技能。肥胖已经达到流行病的程度，最成功的持续减肥方法是减肥手术。尽管减肥手术在总体上具有无可争议的有效性，但治疗反应仍存在显著的个体间差异。这些减肥手术导致人类体重减轻的机制仅部分了解。更好地了解减肥手术患者体重减轻的潜在机制将有助于改善治疗和结局。我的假设是，减肥手术后的体重减轻部分是由于食物偏好的改变和口味的变化。我计划 研究在垂直袖状胃切除术（VSG，n = 20）或Roux-en Y胃旁路术（RYGB，n = 20）之前和之后对不同浓度的蔗糖和含脂肪刺激物的味觉反应，以及在使用饮食诱导的体重减轻的对照组（n = 20）中。参与者将在干预前2周和1周以及干预后2周、3个月、6个月和12个月进行评估。对不同水平的蔗糖和含脂肪刺激物的味觉偏好将 测量和验证问卷，用于定性确定奖励敏感性，暴饮暴食行为和冲动。将进行功能性磁共振成像（fMRI），以评估大脑奖励区域的神经生物学变化。血氧水平依赖性（BOLD）fMRI信号将用于评估DA介导的奖赏回路（例如纹状体）在手术前一周和手术后两周对蔗糖和含脂肪刺激的反应。这些研究将补充我以前关于多巴胺奖励区域与肥胖关系的工作，增强我们对摄食行为机制的理解。我预计，接受减肥手术干预的患者在手术后立即会有明显的味觉偏好变化，但这种变化不会无限期地持续下去。我们将定义这段口味变化的时期， 体重减轻、味觉改变和特定的神经解剖学大脑活动之间的联系。我相信 这项研究将把术前的味觉偏好与长期的减肥结果联系起来。这项研究的临床意义包括改善减肥手术的减肥效果。

DESCRIPTION (provided by applicant): I am a junior faculty member in the Department of Surgery at the Johns Hopkins University School of Medicine, and a Ph.D. candidate in Clinical Investigation from the Johns Hopkins Bloomberg School of Public Health. My previous work has focused on brain dopamine (DA) alterations in obese patients following gastric bypass. The objective of this mentored research project is to investigate alterations in the neurobiology of taste preference induced by bariatric surgery, and to explore the relationship of taste responsiveness to successful long-term weight loss. While conducting this study I will enhance my research knowledge and skills through formal coursework in nutritional epidemiology, neuroscience, and neuroimaging and through directed research mentorship by a team of experts in behavioral neuroscience, psychiatry, nutrition, epidemiology and surgery. Obesity has reached epidemic proportions and the most successful method of sustained weight loss is bariatric surgery. Despite the indisputable effectiveness of bariatric surgery in the aggregate, there remains significant inter-individual variability in treatment response. The mechanisms by which these bariatric procedures lead to weight loss in humans are only partially understood. A better understanding of the underlying mechanisms of weight loss in the bariatric surgical patient will allow for improved treatments and outcomes. My hypothesis is that weight loss after bariatric surgery is due in part to alterations in food preferences and changes in taste. I plan to investigate taste responses to varying concentrations of sucrose and fat-containing stimuli before and after vertical sleeve gastrectomy (VSG, n=20) or Roux-en Y gastric bypass (RYGB, n=20), as well as in a control group using diet-induced weight loss (n=20). Participants will be assessed at 2 weeks and 1 week prior, and 2 weeks, 3 months, 6 months, and 12 months after the intervention. Taste preferences to varying levels of sucrose and fat-containing stimuli will be measured, and validated questionnaires used to qualitatively determine reward sensitivity, binge eating behavior, and impulsivity. Functional magnetic resonance imaging (fMRI) will be performed to assess neurobiologic changes in reward regions of the brain. Blood-oxygen-level- dependent (BOLD) fMRI signaling will be used to assess DA-mediated reward circuitry (e.g. striatum) in response to sucrose and fat-containing stimuli at one week before and two weeks after surgery. These studies will complement my previous work on the relation of dopamine-based reward regions and obesity, enhancing our understanding of the mechanisms involved in feeding behavior. I expect that patients who undergo a bariatric surgical intervention will have a significant change in taste preference immediately following surgery, but that this change will not persist indefinitely. We will define this period of taste change and determine the relationship between weight loss, taste alterations, and specific neuroanatomical brain activity. I believe that this research will correlate pre-operative taste preference with long term weight loss outcome. The clinical implications of this research include improved weight loss outcomes from bariatric surgery.