Brain Derived Neurotrophic Factor involvement in exercise modulation of appetite

脑源性神经营养因子参与运动调节食欲

• 批准号: 8823318
• 负责人: ChuanFeng Wang
• 金额: --
• 依托单位: MINNEAPOLIS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8823318
• 关键词: Affect; Animal Model; Animals; Appetite Regulation; Body Weight; Body Weight decreased; Brain; Brain-Derived Neurotrophic Factor; Burn injury; Calories; Cell Nucleus; Cell physiology; Cells; Chemicals; Ciliary Neurotrophic Factor; Clinical Treatment; Consumption; Data; Desire for food; Disease; Eating; Eating Disorders; Energy Intake; Energy Metabolism; Exercise; Family; Financial compensation; Food; Goals; Growth Factor; Health; Hippocampus (Brain); Homeostasis; Human; Hypothalamic structure; Incidence; Leptin; Link; Mediating; Messenger RNA; Neurons; Neurotrophic Tyrosine Kinase Receptor Type 2; Obesity; Overweight; Patients; Peptides; Phenotype; Phosphotransferases; Physical activity; Population; Prevalence; Production; Proteins; Rattus; Regulation; Rodent; Role; Running; Serum; Signal Transduction; Site; Testing; Tropomyosin; Veterans; Weight Gain; base; brain cell; cell growth; energy balance; feeding; food consumption; improved; improved functioning; member; neurogenesis; neuronal survival; neurotrophic factor; new growth; obesity prevention; obesity treatment; paraventricular nucleus; prevent; public health relevance; receptor; sedentary

DESCRIPTION (provided by applicant): Disorders of energy metabolism and overweight/obesity are extremely common. Up to 48% of Veterans are overweight and 24% are obese, a higher incidence than that of the general US population. Reductions in physical activity levels as well as an increase in the consumption of energy-dense food have paralleled the increase in obesity prevalence. It is crucial to find approaches to prevent and treat obesity and related health problems. ! Evidence suggests that physical exercise can improve appetite function, so that body weight is better controlled. In addition to increasing energy expenditure (calories burned), exercise is known to reduce appetite. Changed signaling in a brain site (the hypothalamus) has been proposed as a possible mechanism underlying exercise-induced reductions in feeding. We hypothesize that BDNF (brain derived neurotrophic factor), a brain chemical, is involved in exercise-induced feeding reduction. ! We have found that exercise and BDNF share some common effects, as both reduce food intake and body weight, and increase energy expenditure. The amount of BDNF in the hypothalamus seems to affect feeding and energy expenditure: with an increase (or decrease) in hypothalamic BDNF, food consumption is decreased (or increased) whereas energy expenditure is increased (or decreased), respectively. In rats, an increase in running elevates BDNF in hypothalamus. Exercise increases hypothalamic BDNF and BDNF-containing cells (neurons) compared to sedentary animals. After we chronically injected BDNF in hypothalamus of rats, there was new cell growth in hypothalamus. This suggests exercise may promote new cell growth by increasing BDNF production. However, the identities of the new cells and the impact of these new cells on energy regulation need to be explored. ! We hypothesize that BDNF mediates exercise-associated reductions in food intake, increases in energy expenditure, and improvement of brain function, and that exercise induces new nerve cells that contribute to regulation of energy balance. To test these ideas, we propose these aims: ! Aim 1. Exercise increases BDNF action in hypothalamus, reducing food intake and body weight. In this aim we will test whether exercise increases BDNF action and reduces food intake, and whether BDNF is necessary for exercise induced feeding reduction. ! Aim 2. Exercise improves hypothalamic function via BDNF. In this aim we will test whether exercise improves function of the hypothalamus, mainly by increasing growth of new nerve cells, and whether BDNF is necessary for exercise-induced cell growth. ! Aim 3. Exercise induced hypothalamic new cells contribute to energy balance regulation. In this aim we will test whether exercise-induced new cells contribute to feeding reduction and energy expenditure increase, determine the identities of the newly developed cells, and whether the exercise-induced new cells respond to proteins important to body weight regulation. ! The results gained will help our efforts in obesity prevention and treatment in our Veteran population.

描述（由申请人提供）： 能量代谢和超重/肥胖症的疾病极为普遍。多达48％的退伍军人超重，有24％的肥胖，比美国普通人口高。体育活动水平的降低以及能量密度食物消耗的增加与肥胖症患病率的增加相似。找到预防和治疗肥胖和相关健康问题的方法至关重要。 呢 有证据表明，体育锻炼可以改善食欲功能，从而更好地控制体重。除了增加能量消耗（燃烧的卡路里）外，还已知运动可以减少食欲。已经提出，已经提出了大脑部位（下丘脑）的信号传导，作为运动引起的喂养减少的可能机制。我们假设BDNF（脑衍生的神经营养因子）是一种脑化学物质，参与了运动引起的进食降低。 呢 我们发现运动和BDNF具有一些共同的影响，因为既减少食物摄入量和体重，又可以增加能量消耗。下丘脑中BDNF的量似乎会影响喂养和能量消耗：下丘脑BDNF的增加（或减少），食物消耗减少（或增加），而能源消耗分别增加（或减少）。在大鼠中，下丘脑的跑步升高会增加BDNF。与久坐的动物相比，运动增加了下丘脑BDNF和含BDNF的细胞（神经元）。在大鼠下丘脑中长期注射BDNF后，下丘脑有新的细胞生长。这表明运动可以通过增加BDNF产生来促进新的细胞生长。但是，需要探索新细胞的身份以及这些新细胞对能量调节的影响。 呢 我们假设BDNF介导了与运动相关的食物摄入量减少，能量消耗的增加和脑功能的改善，并且锻炼会引起有助于调节能量平衡的新神经细胞。为了测试这些想法，我们提出了这些目标：！目标1。运动增加了下丘脑中的BDNF作用，减少了食物摄入和体重。在此目标中，我们将测试运动是否会增加BDNF的作用并减少食物摄入量，以及是否需要BDNF进行运动诱导的减少喂养。呢AIM 2。锻炼通过BDNF改善下丘脑功能。在此目标中，我们将测试运动是否改善下丘脑的功能，主要是通过增加新神经细胞的生长以及BDNF是否是运动诱导的细胞生长所必需的。呢目标3。运动诱导的下丘脑新细胞有助于能量平衡调节。在此目标中，我们将测试运动引起的新细胞是否有助于减少和能量消耗的增加，确定新开发的细胞的身份，以及运动诱导的新细胞是否对对体重调节重要的蛋白质有反应。呢获得的结果将有助于我们在退伍军人人群中进行预防和治疗的努力。