Effect of Insulin on Brain Activation, Food Craving, and Food Intake in Obesity

描述(申请人提供)：K23研究研究的目的是确定胰岛素水平增加影响与食物奖励-动机有关的大脑区域并影响饮食行为的机制。这项研究将为研究新的治疗方法提供必要的关键数据，这些治疗方法旨在减轻高胰岛素血症对大脑的影响，以遏制对食物的渴望和过量的能量摄入，从而减少体重增加。本研究项目的具体目的是研究胰岛素对心脏的影响。 研究超重/肥胖和瘦个体对食物提示和饮食行为的神经反应，并评估胰岛素抵抗对这些神经机制和食物摄入量的影响。这项研究是一项横断面的实验研究，评估奖励动机、决策和脑内平衡区域对急性外周注射胰岛素的神经反应。在接受高胰岛素-正常血糖钳夹与生理盐水-正常血糖对照的同时，将进行功能磁共振成像(FMRI)扫描，以评估30名超重/肥胖和20名瘦人在观看高卡路里食物图片时的神经反应。50名受试者中的每一位都将在两天内以随机方式接受高胰岛素-正常血糖-和生理盐水-正常血糖功能磁共振检查。在整个实验过程中，将评估对食物的渴望和饥饿感，并将在高胰岛素-正常血糖-和盐水-正常血糖-功能磁共振程序之后测量食物摄入量。胰岛素抵抗对观察到的神经反应和饮食行为的作用也将被调查。这项研究的结果将为深入了解胰岛素如何影响神经提供依据。 肥胖和瘦削个体的胰岛素抵抗机制和饮食行为，并有助于确定胰岛素抵抗在这些机制中可能发挥的作用。这项研究将有助于理解肥胖的病理生理机制，并有可能通过阐明减轻对食物的渴望和高热量食物的摄入的治疗目标来影响肥胖症和2型糖尿病的干预。此外，拟议的项目和重要的行为神经学培训将为应聘者提供成功申请R01所需的数据和知识。这项提案的目标与《美国国立卫生研究院肥胖研究战略计划》的目标是一致的，该战略计划的目的是“发现调节体重和影响行为的基本生物过程”，并“了解导致肥胖的因素及其后果”。阐明胰岛素如何影响肥胖个体的神经机制和饮食行为，并确定胰岛素抵抗和高胰岛素血症在这些机制中可能发挥的作用，将有助于理解肥胖和高热量食物消费的病理生理机制，以及潜在地影响肥胖症和2型糖尿病的治疗干预。

DESCRIPTION (provided by applicant): The purpose of the K23 research study is to define the mechanisms by which increased levels of insulin affect brain regions involved in food reward-motivation and influence eating behavior. This study will provide critical data necessary for the investigation of novel treatments that target attenuating the effects of hyperinsulinemia on the brain, in order to curb food cravings and excess energy intake, thereby diminishing weight gain. The specific aims of this research project are to investigate the effect of insulin on neural responses to food cues and eating-behaviors in overweight/obese and lean individuals and to assess the influence insulin resistance has on these neural mechanisms and food intake. The study is a cross-sectional, experimental study assessing neural responses in reward-motivation, decision-making, and homeostatic brain regions in response to acute, peripheral administration of insulin. While undergoing hyperinsulinemic-euglycemic clamp vs. saline-euglycemic control, functional magnetic resonance imaging (fMRI) scans will be conducted to assess neural responses in 30 overweight/obese and 20 lean individuals during viewing of high-calorie food pictures. Each of the 50 subjects will undergo hyperinsulinemic-euglycemic- and saline-euglycemic- fMRI procedures in randomized fashion on two separate days. Food craving and hunger will be assessed throughout the experiment and food intake will be measured following both the hyperinsulinemic-euglycemic- and saline- euglycemic- fMRI procedures. The role of insulin resistance on the observed neural responses and on eating behavior will also be investigated. Results obtained from this study will provide insight into how insulin affects neural mechanisms and eating behaviors in obese and lean individuals and help determine the role insulin resistance may play in these mechanisms. This study will contribute to the understanding of pathophysiologic mechanisms involved in obesity and has the potential to impact interventions for obesity and type 2 diabetes by elucidating therapeutic targets to attenuate food craving and intake of high-calorie foods. Additionally, the proposed project and vital behavioral-neuroscience training will provide the candidate with the data and knowledge required for a successful R01 application. The goals of this proposal are consistent with the Strategic Plan for NIH Obesity Research to "discover fundamental biological processes that regulate body weight and influence behavior" and to "understand the factors that contribute to obesity and its consequences". Elucidating how insulin affects neural mechanisms and eating behaviors in obese individuals and determining the role insulin resistance and hyperinsulinemia may play in these mechanisms will significantly contribute to understanding pathophysiologic mechanisms involved in obesity and high-calorie food consumption, as well as potentially impact therapeutic interventions for obesity and type 2 diabetes.