Brain Derived Neurotrophic Factor involvement in exercise modulation of appetite

描述(由申请人提供)： 能量代谢紊乱和超重/肥胖是非常常见的。高达48%的退伍军人超重，24%的退伍军人肥胖，这一比例高于美国普通人群。体力活动水平的减少以及高能量食物消费的增加与肥胖率的增加是平行的。找到预防和治疗肥胖症及相关健康问题的方法至关重要。好了！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，运动还会降低食欲。大脑部位(下丘脑)的信号变化被认为是运动导致进食减少的可能机制。我们假设脑源性神经营养因子(脑源性神经营养因子)，一种大脑化学物质，与运动诱导的摄食减少有关。好了！我们发现，运动和脑源性神经营养因子有一些共同的效果，因为它们都减少了食物的摄入量和体重，并增加了能量消耗。下丘脑中BDNF的数量似乎影响摄食和能量消耗：随着下丘脑BDNF的增加(或减少)，食物消耗减少(或增加)，而能量消耗增加(或减少)。在大鼠中，跑步增加会增加下丘脑中的BDNF。与久坐不动的动物相比，运动增加了下丘脑BDNF和含有BDNF的细胞(神经元)。大鼠下丘脑慢性注射BDNF后，下丘脑有新的细胞生长。这表明运动可能通过增加BDNF的产生来促进新细胞的生长。然而，新细胞的身份以及这些新细胞对能量调节的影响还需要探索。好了！我们假设BDNF介导了运动相关的食物摄入量的减少、能量消耗的增加和大脑功能的改善，运动诱导了有助于调节能量平衡的新的神经细胞。为了检验这些想法，我们提出了以下目标：！目的1.运动增加下丘脑BDNF的作用，减少摄食量和体重。在这一目标中，我们将测试运动是否增加BDNF的作用并减少食物摄入量，以及BDNF是否对于运动诱导的摄食减少是必要的。好了！目的2.运动通过脑源性神经营养因子改善下丘脑功能。在这一目标中，我们将测试运动是否主要通过促进新神经细胞的生长来改善下丘脑的功能，以及BDNF是否对运动诱导的细胞生长是必需的。好了！目的3.运动诱导的下丘脑新细胞参与能量平衡调节。为此，我们将测试运动诱导的新细胞是否有助于减少摄食和增加能量消耗，确定新发育的细胞的身份，以及运动诱导的新细胞是否对体重调节重要的蛋白质做出反应。好了！取得的成果将有助于我们在退伍军人中预防和治疗肥胖症的努力。

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.