Brain Mechanisms of Non-Exercise Activity Thermogenesis

非运动活动产热的大脑机制

• 批准号: 7421022
• 负责人: Colleen M Novak
• 金额: $ 33.44万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7421022
• 关键词: Affect; Animals; Appendix; Arousal; Behavioral; Body Weight; Body Weight decreased; Body fat; Brain; Brain region; Carbohydrates; Daily; Diet; Energy Intake; Energy Metabolism; Exercise; Face; Fatty acid glycerol esters; Habits; Health; Hormonal; Hour; Human; Hypothalamic structure; Individual Differences; Injection of therapeutic agent; Lateral; Life Style; Mediating; Mediator of activation protein; Messenger RNA; Molecular Genetics; Neuropeptides; Obesity; Physical activity; Population; Positioning Attribute; Publications; Rat Strains; Rate; Rattus; Research Personnel; Resistance; Role; Satiation; Signal Transduction; Societies; Sprague-Dawley Rats; Standards of Weights and Measures; System; Thermogenesis; Time; United States; Week; Weight; Weight Gain; energy balance; feeding; hypocretin; neuromechanism; orexin A; paraventricular nucleus; programs; relating to nervous system; sedentary

DESCRIPTION (provided by applicant): Obesity is a growing health concern. As obesity has increased, the amount of physical activity in the population has decreased. In our sedentary society, low levels of physical activity have a significant impact on weight gain. Whereas the neural, hormonal, molecular, and genetic mechanisms of energy intake are well studied, very little is known about the mechanisms through which energy is expended through physical activity. Non-exercise activity thermogenesis (NEAT) in humans is comprised of the energy expenditure of all physical activity outside of volitional exercise; NEAT contributes significantly to the ability to resist weight gain in the face of overfeeding. We have previously demonstrated that central administration of the neuropeptide orexin A increases NEAT in rats. Moreover, obesity-prone rats are less sensitive to the NEAT-activating effects of orexin in the paraventricular hypothalamic nucleus (PVN) after access to a high-fat diet compared to obesity-resistant rats. Here, we propose to systematically examine the mechanisms through which PVN orexin differentially affects NEAT in obese and lean animals. We hypothesize that the energy expenditure from orexin-induced NEAT induces weight loss. Therefore, we will determine if twice-daily central orexin treatment decreases body weight and increases NEAT in rats. Next, we hypothesize that decreases in orexin-induced NEAT contribute to weight gain in obesity-prone rats. Therefore, in the second study, we will determine how the high-fat diet contributes to the ability of orexin to stimulate NEAT in the obesity-prone, obesity-resistant, and control rats. Third, we will determine how a high-carbohydrate diet alters daily NEAT in obesity-prone, obesity-resistant, and control rats, as well as how the diet affects orexin-induced NEAT. Lastly, we will examine the neural mechanisms of the differential effects of orexin on NEAT in obesity-prone, obesity- resistant, and control rats by comparing orexin synthesis and orexin content in targeted brain regions in these animals. With these studies, we hope to delineate the neural mechanisms of how orexin affects changes in NEAT, as well as to assess how orexin interacts with diet to affect NEAT and obesity. Understanding the mechanisms through which the energy expenditure of physical activity affects NEAT is a critical step in developing effective behavioral and pharmacological strategies to combat obesity.

描述（由申请人提供）：肥胖是一个日益严重的健康问题。随着肥胖症的增加，人群的体育锻炼量减少。在我们久坐的社会中，低水平的体育活动对体重增加有重大影响。很好地研究了能量摄入的神经，激素，分子和遗传机制，但对通过体育活动消耗能量的机制知之甚少。人类中的非运动活性热发生（整洁）由自愿运动以外的所有体育活动的能量消耗组成；面对过度喂养，整洁有助于抵抗体重增加的能力。我们以前已经证明，神经肽OREXIN A的中央给药会增加大鼠的整齐。此外，与耐肥胖大鼠相比，易肥胖的大鼠在接受高脂饮食后，对脑室下丘脑核（PVN）的整洁激活作用的敏感性较小。在这里，我们建议系统地检查PVN Orexin差异影响肥胖动物整洁的机制。我们假设来自Orexin诱导的纯净的能量消耗会诱导体重减轻。因此，我们将确定每天两次中枢Orexin治疗是否会降低体重并增加大鼠的整洁。接下来，我们假设Orexin诱导的整齐的降低会导致肥胖易发的大鼠体重增加。因此，在第二项研究中，我们将确定高脂饮食如何促进奥雷蛋白刺激肥胖，抗肥胖症和控制大鼠整洁的能力。第三，我们将确定高碳水化合物饮食如何在易肥胖，耐心和控制大鼠的每日整洁，以及饮食如何影响Orexin引起的整洁。最后，我们将通过比较这些动物的靶向大脑区域中的Orexin Synthesis和Orexin含量来检查Orexin对肥胖，肥胖和控制大鼠整洁的差异作用的神经机制。通过这些研究，我们希望描述奥甲蛋白如何影响整洁变化的神经机制，并评估奥列海素如何与饮食相互作用以影响整洁和肥胖。了解体育锻炼能量消耗整洁的机制是制定有效的行为和药理策略来打击肥胖的关键步骤。