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

描述（由申请人提供）：K23研究的目的是确定胰岛素水平升高影响食物奖励动机相关脑区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，以抑制食物渴望和过量能量摄入，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 超重/肥胖和瘦个体对食物线索和进食行为的神经反应，并评估胰岛素抵抗对这些神经机制和食物摄入的影响。本研究是一项横断面实验研究，评估急性外周胰岛素给药后奖励动机、决策和稳态脑区的神经反应。在进行高胰岛素-正常血糖钳夹与生理盐水-正常血糖控制的同时，将进行功能性磁共振成像（fMRI）扫描，以评估30名超重/肥胖和20名瘦个体在观看高热量食物图片期间的神经反应。50名受试者中的每一名将在两个不同的日子以随机方式接受高胰岛素-血糖正常-和生理盐水-血糖正常- fMRI程序。将在整个实验中评估食物渴望和饥饿，并在高胰岛素-血糖正常-和盐水-血糖正常- fMRI程序后测量食物摄入。还将研究胰岛素抵抗对观察到的神经反应和饮食行为的作用。从这项研究中获得的结果将提供深入了解胰岛素如何影响神经 肥胖和瘦个体的胰岛素抵抗机制和饮食行为，并帮助确定胰岛素抵抗在这些机制中可能发挥的作用。这项研究将有助于了解肥胖症的病理生理机制，并有可能通过阐明治疗目标来影响肥胖症和2型糖尿病的干预措施，以减轻对食物的渴望和高热量食物的摄入。此外，拟议的项目和重要的行为神经科学培训将为候选人提供成功申请R 01所需的数据和知识。该提案的目标与NIH肥胖研究战略计划一致，即“发现调节体重和影响行为的基本生物学过程”，并“了解导致肥胖及其后果的因素”。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，将大大有助于了解肥胖和高热量食物消耗的病理生理机制，以及可能影响肥胖和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.