Does early overnutrition differentially alter hypothalamic neuropeptides that regulate food intake in the rat

早期营养过剩是否会差异性地改变调节大鼠食物摄入的下丘脑神经肽

• 批准号: nhmrc : 299875
• 负责人: Prof Margaret Morris
• 金额: $ 23.09万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/does-early-overnutrition-intake-rat/82732
• 关键词: Does; early; overnutrition; differentially; alter

In Australia the incidence of obesity, in particular childhood obesity, is increasing dramatically, and the possible long term consequences of this are of great concern. The brain regulates appetite through a number of chemical transmitters such as neuropeptide Y (NPY) which is present in the brains of mammals and causes increased food intake. The effects of overeating from a young age on these brain transmitters has been largely ignored although this may impact on subsequent eating behaviour. In addition to NPY we will study other transmitters in the brain that have profound effects on appetite, some increasing, and others decreasing, food intake. These may form useful therapeutic targets for new drugs for obesity. Key targets we will study include melanocortins, glucagon-like peptide 1, urocortin, melanin concentrating hormone, agouti related peptide, and NPY. We will determine whether overnutrition from birth to weaning leads to changes in these appetite regulating neurotransmitters in the brain, and monitor the hormonal signals that impact on their activity. We will also determine whether early overnutrition exacerbates the subsequent responses to a high fat diet by comparison with rats made obese as adults. We will measure brain concentrations of the neurotransmitters, the amount released from the brain, and determine whether the feeding responses to injections of these agents is altered in obese animals. We have evidence that these transmitters interact in a co-ordinated fashion to affect feeding; this project will examine whether these interactions are maintained in the various types of obesity. Rats are commonly used for this type of study as the processes regulating feeding are very similar to those in humans and these agents cause similar effects in rats and humans. It is hoped that this information will provide new insight into the way brain adapts to overnutrition, and provide potential treatments for obesity and other feeding disorders.

在澳大利亚，肥胖症的发病率，特别是儿童肥胖症，正在急剧增加，其可能的长期后果令人非常担忧。大脑通过许多化学递质调节食欲，如神经肽Y（NPY），它存在于哺乳动物的大脑中，导致食物摄入量增加。从小暴饮暴食对这些大脑递质的影响在很大程度上被忽视了，尽管这可能会影响随后的饮食行为。除了神经肽Y，我们将研究大脑中对食欲有深远影响的其他递质，一些增加，另一些减少食物摄入。这些可能会成为治疗肥胖症的新药的有用的治疗靶点。我们将研究的主要靶点包括黑皮质素、胰高血糖素样肽1、尿皮质素、黑色素浓集激素、聚集素相关肽和NPY。我们将确定从出生到断奶的营养过剩是否会导致大脑中这些食欲调节神经递质的变化，并监测影响其活动的激素信号。我们还将通过与成年肥胖大鼠的比较，确定早期营养过剩是否会加剧随后对高脂肪饮食的反应。我们将测量大脑中神经递质的浓度，从大脑中释放的量，并确定肥胖动物对这些药物注射的进食反应是否改变。我们有证据表明，这些递质以协调的方式相互作用，影响进食;这个项目将研究这些相互作用是否在各种类型的肥胖中保持。大鼠通常用于这种类型的研究，因为调节进食的过程与人类非常相似，并且这些药物在大鼠和人类中引起相似的影响。希望这些信息将为大脑适应营养过剩的方式提供新的见解，并为肥胖和其他喂养障碍提供潜在的治疗方法。