Brain Mechanisms of Non-Exercise Activity Thermogenesis

非运动活动产热的大脑机制

• 批准号: 7251566
• 负责人: Colleen M Novak
• 金额: $ 32.63万
• 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/7251566
• 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。随着肥胖的增加，人们的体力活动量减少了。在我们久坐的社会中，低水平的体力活动会对体重增加产生重大影响。尽管能量摄入的神经、激素、分子和遗传机制已得到充分研究，但人们对通过体力活动消耗能量的机制知之甚少。人类的非运动活动产热（NEAT）包括意志运动之外的所有身体活动的能量消耗； NEAT 显着提高了在过度喂养时抵抗体重增加的能力。我们之前已经证明，神经肽食欲素 A 的中枢给药会增加大鼠的 NEAT。此外，与肥胖抗性大鼠相比，肥胖倾向大鼠在接受高脂肪饮食后，对室旁下丘脑核（PVN）中食欲素的 NEAT 激活作用不太敏感。在这里，我们建议系统地研究 PVN 食欲素对肥胖和瘦动物中 NEAT 的差异影响的机制。我们假设食欲素诱导的 NEAT 的能量消耗会导致体重减轻。因此，我们将确定每日两次中枢食欲素治疗是否会降低大鼠体重并增加 NEAT。接下来，我们假设食欲素诱导的 NEAT 减少会导致肥胖大鼠体重增加。因此，在第二项研究中，我们将确定高脂肪饮食如何促进易肥胖、抗肥胖和对照大鼠中食欲素刺激 NEAT 的能力。第三，我们将确定高碳水化合物饮食如何改变易肥胖、抗肥胖和对照大鼠的日常 NEAT，以及饮食如何影响食欲素诱导的 NEAT。最后，我们将通过比较这些动物目标大脑区域的食欲素合成和食欲素含量，研究食欲素对易肥胖、抗肥胖和对照大鼠的 NEAT 产生不同影响的神经机制。通过这些研究，我们希望描绘出食欲素如何影响 NEAT 变化的神经机制，并评估食欲素如何与饮食相互作用以影响 NEAT 和肥胖。了解身体活动的能量消耗影响 NEAT 的机制是制定有效的行为和药理学策略来对抗肥胖的关键一步。