Neural Functioning of Feeding Centers in Obese Youth

肥胖青少年喂养中心的神经功能

基本信息

批准号：
8610296
负责人：
SONIA CAPRIO
金额：
$ 51.08万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8610296
关键词：
Acute Adolescence Adolescent Adult Affect Age American Amygdaloid structure Animal Model Animals Attenuated Automobile Driving Behavior Bilateral Biological Markers Blood flow Body Weight Changes Brain Brain region Cerebrovascular Circulation Child Childhood Clinical Complex Consumption Corpus striatum structure Coupled Cues Deposition Desire for food Development Diabetes Mellitus Diagnostic radiologic examination Diet Disease Dopamine Dorsal Dyslipidemias Eating Energy Intake Energy Metabolism Epidemiology Exhibits Fatty acid glycerol esters Feeding behaviors Female Adolescents Food Fructose Functional Magnetic Resonance Imaging Functional disorder Fusiform gyrus Gender Glucose Glucose Intolerance Goals High Prevalence Homeostasis Hormones Hunger Hyperinsulinism Hyperphagia Hypothalamic structure Inflammation Ingestion Insula of Reil Insulin Insulin Resistance Intake Internal Medicine Investigation Lead Leptin Link Lipids Longitudinal Studies Magnetic Resonance Imaging Malonyl Coenzyme A Maps Measurement Measures Mediating Metabolic Metabolic syndrome Neurons Neurophysiology - biologic function Non obese Non-Insulin-Dependent Diabetes Mellitus Nutrient Obesity Oral Parahippocampal Gyrus Pediatrics Peripheral Phenotype Physiological Play Population Prediabetes syndrome Prevalence Prospective Studies Psychiatry Puberty Public Health Regulation Relative (related person)Reporting Research Research Personnel Resistance Rest Rewards Risk Risk Factors Role Satiation Scientist Secondary to Series Severities Signal Transduction Source Staging Subgroup Sweetening Agents System Time Translating Ventral Striatum Visceral Weight Gain Work Youth adenylate kinase adiponectin base caudate nucleus cohort critical period diabetes prevention program endophenotype fasting glucose feeding ghrelin girls glucose metabolism glucose tolerance hedonic impaired glucose tolerance insight insulin secretion insulin sensitivity intrahepatic male multidisciplinary neural circuit neurobehavioral obesity in children patient oriented research public health relevance research study response reward circuitry subcutaneous

项目摘要

DESCRIPTION (provided by applicant): Adolescent obesity is fueling the increase in the prevalence of T2DM in youth. Obese adolescents on their path to developing prediabetes/T2DM present with severe peripheral insulin resistance, marked hyperinsulinemia and relatively low leptin levels. These abnormal adiposity related signals may not only favor the development of peripheral but also central insulin resistance, thereby promoting the perpetuation of obesity and its associated metabolic complications. Dr. Caprio's research is mainly in peripheral insulin and glucose metabolism in obese adolescents. However, there are a number of basic, clinical, physicist and neurobehavioral scientists at Yale actively working in the field of Central Regulation of Energy Metabolism. Our goal is to bring together these various Yale-based investigators to explore whether obese adolescents with insulin resistance and relative low leptin levels exhibit functional alterations of the neuronal circuits involved in the regulation of energy metabolism and food seeking behaviors. We here propose a series of hypotheses-driven studies which will be performed by a multidisciplinary team of investigators from Internal Medicine, Diagnostic Radiology, Psychiatry and Pediatrics, using an integrated team approach. The hypotheses are: 1- The hypothalamic fMRI signal after the ingestion of glucose is attenuated in obese adolescents with insulin resistance, relative low levels of leptin and marked hyperinsulinemia compared to age, gender and puberty matched obese sensitive and lean adolescents. 2- Fructose consumption has differential effects when compared to glucose on the functional connections between the hypothalamus and other brain regions implicated in feeding behavior and that these differential effects are magnified in obese adolescents. 3- Functional connectivity between brain regions of the reward system implicated in the response to specific food cues are altered in the obese adolescents and this is related to hyperinsulinemia/insulin resistance. The team will use functional connectivity fMRI mapping to examine the connections between specific appetitive regions such as the dorsal striatum and caudate nucleus and the hypothalamus. In particular, we will examine how connectivity within these networks changes as a function of brain fuel, and we will look for differential network responses to the fuels between lean and obese adolescents with extreme ends of the insulin resistance spectrum. Understanding the differential response of centers regulating the homeostatic and non-homeostatic neuronal circuits to common highly palatable foods (glucose) in obese adolescents may translate into the development of more effective weight gain and diabetes prevention program in youth.

描述（由申请人提供）：青少年肥胖正在加剧青少年 T2DM 患病率的增加。正在发展为糖尿病前期/T2DM 的肥胖青少年会出现严重的外周胰岛素抵抗、明显的高胰岛素血症和相对较低的瘦素水平。这些异常的肥胖相关信号可能不仅有利于外周胰岛素抵抗的发展，而且有利于中枢胰岛素抵抗的发展，从而促进肥胖及其相关代谢并发症的持续存在。卡普里奥博士的研究主要是肥胖青少年的外周胰岛素和葡萄糖代谢。然而，耶鲁大学有许多基础、临床、物理学和神经行为科学家积极致力于能量代谢的中央调节领域。我们的目标是将耶鲁大学的这些不同的研究人员聚集在一起，探讨具有胰岛素抵抗和瘦素水平相对较低的肥胖青少年是否表现出参与调节能量代谢和食物寻求行为的神经元回路的功能改变。我们在这里提出了一系列假设驱动的研究，这些研究将由来自内科、诊断放射学、精神病学和儿科的多学科研究小组采用综合团队方法进行。假设是： 1-与年龄、性别和青春期相匹配的肥胖敏感和瘦的青少年相比，具有胰岛素抵抗、瘦素水平相对较低和明显高胰岛素血症的肥胖青少年摄入葡萄糖后下丘脑功能磁共振成像信号减弱。 2- 与葡萄糖相比，果糖摄入对下丘脑和与进食行为有关的其他大脑区域之间的功能连接具有不同的影响，并且这些不同的影响在肥胖青少年中被放大。 3-肥胖青少年中与对特定食物线索的反应有关的奖励系统大脑区域之间的功能连接发生了改变，这与高胰岛素血症/胰岛素抵抗有关。该团队将使用功能连接功能磁共振成像图来检查特定食欲区域（例如背侧纹状体和尾状核）与下丘脑之间的连接。特别是，我们将研究这些网络内的连接如何随着大脑燃料的变化而变化，并且我们将寻找具有胰岛素抵抗谱极端的瘦青少年和肥胖青少年之间对燃料的差异网络反应。了解肥胖青少年中调节稳态和非稳态神经元回路的中心对常见高适口食物（葡萄糖）的差异反应可能有助于制定更有效的青少年体重增加和糖尿病预防计划。