Autonomic Regulation of Food Intake and Metabolism

食物摄入和代谢的自主调节

• 批准号: 6853599
• 负责人: HANS-RUDOLF BERTHOUD
• 金额: $ 30.03万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-20 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6853599
• 关键词: afferent nerve; autonomic nervous system; bioenergetics; biological signal transduction; brain stem; confocal scanning microscopy; eating; hypothalamus; immunocytochemistry; in situ hybridization; laboratory rat; melanocyte stimulating hormone; metabolism; mitogen activated protein kinase; neural transmission; neurochemistry; neuroendocrine system; neurons; neurophysiology; phosphorylation; satiations; secretory protein; weight control agent; western blottings

DESCRIPTION (provided by applicant): A balanced control of food intake and energy expenditure is required to keep body weight in the normal range and to avoid development of obesity, which has reached epidemic proportions and is associated with costly secondary health problems. Neural circuits in the caudal brainstem are thought to play a key role in the control of food intake and energy balance, as they receive information from the alimentary canal and organize the necessary motor patterns for oropharyngeal and autonomic responses. The basic assumption of this proposal is that other key circuits in the hypothalamus, carrying longer-term metabolic and cognitive information, modulate caudal brainstem circuits concerned primarily with short-term reflex action, to achieve overall homeostatic regulation. Preliminary work by us and others has shown that (1) hypothalamic neurons expressing the "feeding peptides" melanocyte-stimulating hormone (a-MSH) and to a lesser extent agouti-related protein (AgRP), project to neurons in the caudal brainstem that receive gut signals and highly express melanocortin MC4- receptors, and (2) alpha-MSH and AgRP and their stable analogs applied directly to the caudal brainstem modulate food intake and meal size, as well as electrophysiological properties and intracellular signaling in neurons of the solitary nucleus and vagal motor nucleus. Now we propose to investigate the neurophysiological mechanisms by which alpha-MSH and AgRP modulate basic brainstem processes of ingestive control. In three specific aims we will focus on (1) the effects of the two peptides on meal structure and satiety mechanisms, (2) the connectivity and neurochemistry of the descending a-MSH and AgRP projections and the recipient neurons in the dorsal vagal complex, and (3) the neurophysiological and molecular mechanisms underlying the integration of visceral vagal and hypothalamic signals leading to changes in satiation and food intake. Our multidimensional approach using state-of-the-art behavioral, anatomical, as well as in vivo and in vitro electrophysiological and molecular techniques will provide crucial information about regulation of energy balance and will help develop therapies to prevent or combat obesity.

描述（由申请人提供）：需要平衡控制食物摄入和能量消耗，以将体重保持在正常范围内，并避免肥胖症的发展，肥胖症已达到流行病的程度，并与昂贵的继发性健康问题相关。尾侧脑干中的神经回路被认为在控制食物摄入和能量平衡中起关键作用，因为它们从消化道接收信息并组织口咽和自主反应所需的运动模式。这一提议的基本假设是，下丘脑中的其他关键回路携带长期代谢和认知信息，调节主要与短期反射活动有关的尾侧脑干回路，以实现整体稳态调节。 我们和其他人的初步工作表明：（1）表达“摄食肽”促黑素细胞激素（α-MSH）和较小程度上的刺鼠相关蛋白（AgRP）的下丘脑神经元投射到尾侧脑干中接收肠道信号并高度表达黑皮质素MC 4受体的神经元，和（2）α-MSH和AgRP及其稳定类似物直接应用于尾脑干调节食物摄入和膳食量，以及孤束核和迷走神经运动核神经元的电生理特性和细胞内信号传导。 现在，我们建议调查的神经生理机制，α-MSH和AgRP调制的基本脑干过程的摄食控制。在三个具体的目标，我们将集中在（1）两种肽对膳食结构和饱腹感机制的影响，（2）下行的α-MSH和AgRP投射和受体神经元在背迷走神经复合体的连接和神经化学，和（3）内脏迷走神经和下丘脑信号的整合，导致饱腹感和食物摄入的变化的神经生理学和分子机制。我们采用最先进的行为、解剖以及体内和体外电生理和分子技术的多维方法将提供有关能量平衡调节的关键信息，并将有助于开发预防或对抗肥胖的疗法。