Sensory Controls of Hyperphagia in Obesity

肥胖症患者食欲过盛的感觉控制

• 批准号: 7886092
• 负责人: GARY J SCHWARTZ
• 金额: $ 4.81万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-15 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7886092
• 关键词: Address; Affect; Behavior Control; Behavioral; Body Weight; Brain; Child; Cholecystokinin; Classification; Congestive Heart Failure; Development; Diabetes Mellitus; Diet; Disease; Dose; Eating; Energy Intake; Epidemic; Evaluation; Exhibits; FOS gene; Feedback; Feeding behaviors; Food; Food Processing; Frequencies; Genetic; Hyperphagia; Hypertension; Infusion procedures; Ingestion; Leptin; Liquid substance; Longevity; Mediating; Metabolic Control; Mus; National Health and Nutrition Examination Survey; Neuraxis; Neurons; Nutrient; Obesity; Oral; Pattern; Peptide Signal Sequences; Peptides; Peripheral; Phenotype; Population; Process; Property; Public Health; Rattus; Recommendation; Regulation; Relative (related person); Research Design; Research Personnel; Risk; Rodent Model; Role; Satiation; Sensory; Signal Pathway; Signal Transduction; Site; Stimulus; Stomach; Sweetening Agents; Therapeutic; Transgenic Organisms; United States; Work; age group; db/db mouse; design; energy balance; feeding; gastrointestinal; leptin receptor; man; mouse model; neurochemistry; neuronal patterning; neurophysiology; obesity prevention; oral sensory; relating to nervous system; research study; response; sham feeding; sugar

DESCRIPTION (provided by applicant): Understanding energy balance and body weight regulation requires an understanding of the behavioral and neural evaluation of the oral and post-oral sensory signals involved in the control of food intake within a meal, as well as signals related to the availability of stored fuels. Obesity represents an important dysfunctional state of energy balance, and is frequently accompanied by hyperphagia that is manifested by increased meal size. Two mouse models of obesity, the ob/ob mouse lacking leptin, and the db/db mouse, lacking functional leptin receptors (LEPR-B), are also hyperphagic, and exhibit increased meal size without altered meal frequency relative to wild type lean controls. In the proposed studies, we outline behavioral and immunocytochemical studies designed to elucidate the role of leptin signaling in determining the oral and post-oral sensory influences on ingestion in obesity. These experiments will: 1) characterize the ability of oral and upper gastrointestinal (GI) food stimuli to affect food intake within a meal, 2) assess the degree to which genetic leptin signaling deficiency interferes with the feedback potency of oral and upper GI signals in the control of meal size, and 3) characterize the patterns of central nervous system activation excited by oral and GI stimuli that affect meal size in mice with alterations in leptin signaling. We will focus on the C57B6J mouse as the background strain for these studies because: 1) it is has a well-described tendency toward dietary obesity and, 2) it is the background strain for ob/ob and db/db mice. We will evaluate: 1) the ability of leptin to modify the feedback potency of oral and GI food stimuli in ob/ob mice, 2) the ability of transgenic neuron-specific replacement of LEPR-B to restore normal processing of oral and GI food stimuli in db/db mice, and 3) the effect of central vs. peripheral inducible LEPR-B deficiency on eating in mice. To identify central neuronal regions important in leptin's ability to modulate the processing of food stimuli, we will also evaluate the central nervous system patterns of c-Fos expression in these strains in response to selective oral and/or GI food stimuli. This systematic assessment of meal-related stimuli, their central neural representation, and their integration with energy balance peptide signals will significantly advance our understanding of neuro-humoral interactions in the metabolic control of food intake.

描述（由申请人提供）：了解能量平衡和体重调节需要了解对食物摄入量中涉及的口腔和口腔和后感觉信号的行为和神经评估，以及与此相关的信号储存燃料的可用性。肥胖代表了能量平衡的重要功能失调状态，并且经常伴随着由粉状大小增加表现出的倍率。两种小鼠肥胖模型，缺乏瘦素的OB/OB小鼠和缺乏功能性瘦素受体（LEPR-B）的DB/DB小鼠也是倍感，并且相对于野生型精益控制，粉状大小没有变化而没有改变的粉状频率。在拟议的研究中，我们概述了旨在阐明瘦素信号传导在确定口服和后感觉后感觉对肥胖症摄入的口服和后感觉影响的作用的行为和免疫细胞化学研究。这些实验将：1）表征口服和上胃肠道（GI）食物刺激影响一餐中食物摄入量的能力，2）评估遗传瘦素信号缺乏症的程度饮食大小的控制和3）表征了中枢神经系统激活的模式，这些模式受到口服和胃肠道刺激的激发，这些刺激会影响小鼠的饮食大小随瘦素信号传导的改变。我们将重点关注C57B6J小鼠作为这些研究的背景菌株，因为：1）它具有饮食肥胖症的很好的趋势，并且，2）它是OB/OB和DB/DB小鼠的背景菌株。我们将评估：1）瘦素改变ob/ob小鼠口服和胃肠道食物刺激的反馈效力的能力，2）转基因神经元特异性替代LEPR-B恢复口服和GI食品正常加工的能力DB/DB小鼠的刺激，3）中央与周围诱导型LEPR-B缺乏对小鼠进食的影响。为了确定对瘦素调节食物刺激加工能力重要的中央神经元区域，我们还将评估这些菌株中C-FOS表达的中枢神经系统模式，以响应选择性口服和/或GI食物刺激。对饮食相关刺激，其中枢神经表示以及与能量平衡肽信号的整合的系统评估将显着提高我们对食物摄入代谢控制的神经疗法相互作用的理解。