Amino acid sensing by hypothalamic tanycytes

下丘脑单胞细胞的氨基酸传感

• 批准号: BB/M022692/1
• 负责人: Nicholas Dale
• 金额: $ 96.24万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM022692%2F1
• 关键词: Amino; acid; sensing; hypothalamic; tanycytes

Nearly two thirds of the UK population is overweight or obese. This excess weight elevates the risk of premature death and a range of illnesses, such as diabetes and stroke, which greatly reduce quality of life. The hypothalamus at the base of the brain controls body weight by regulating food intake (though feelings of hunger and satiety), and also deposition of fat and expenditure of energy (as heat production and activity). Understanding how the brain signals hunger and satiety is one way in which we can start to develop strategies to reduce the incidence of excess weight in the population.The amino acid content of food is a powerful determinant of satiety. When plasma levels of amino acids are high, then so is the feeling of satiety. Amino acids are detected in the brain. So far four different brain regions have been described in which nerve cells respond to variations in the concentrations of amino acids. We propose to examine a 5th mechanism, which is unique as it is not mediated by nerve cells, but rather by specialized glial cells in the hypothalamus called tanycytes. We have already shown that tanycytes respond to amino acids, and that this may be via the activation of a receptor that also occurs in the taste buds of the tongue which is tuned to the "umami flavour" -the taste of L-amino acids. The overall purpose of this project is to understand why tanycytes sense amino acids in the brain and what this information is used for.Our specific aims are to: 1. Characterize the mechanisms by which tanycytes detect and signal amino acid concentration; 2. Determine whether amino acid sensing via tanycytes interacts with other modalities of nutrient sensing in these cells -specifically their ability to sense glucose; 3. Test whether the properties of amino acid sensing via tanycytes can be altered by diet (fasting, amount of amino acids in food); 4. Examine the contribution of amino acid sensing via tanycytes to determination of food preferences, the amount of food intake, and ultimately control of body weight.Understanding the mechanisms and functional roles of this new amino acid sensing pathway has many benefits for clinicians and related health professionals; commercial organizations; relevant medical charities; government agencies; and the public. Commercial companies may use our work to develop new types of food additive that reduce appetite, or to reformulate food so that it promotes feelings of satiety. In the light of our work, clinicians, dieticians, and relevant medical charities, may be able to modify advice on diet and eating patterns to various classes of patient to promote healthy eating and weight loss. Government agencies may be able to revise their policies with respect to the food industry and advice to the public to promote healthy eating.

英国近三分之二的人口超重或肥胖。这种过多的体重提高了过早死亡的风险和一系列疾病，例如糖尿病和中风，从而大大降低了生活质量。大脑底部的下丘脑通过调节食物摄入（尽管饥饿和饱腹感）以及脂肪的沉积和能量消耗（作为热量产生和活动）来控制体重。了解大脑如何向饥饿和饱腹感信号是我们开始制定策略以减少人口过量体重的发生率的一种方式。食物的氨基酸含量是饱腹感的有力决定因素。当氨基酸的血浆水平很高时，饱腹感也是如此。在大脑中检测到氨基酸。到目前为止，已经描述了四个不同的大脑区域，其中神经细胞对氨基酸浓度的变化反应。我们建议检查第五个机制，该机制是独特的，因为它不是由神经细胞介导的，而是由下丘脑中的专门神经胶质细胞介导的，称为tanycytes。我们已经表明，tanycytes对氨基酸有反应，并且这可以通过激活受体的激活，该受体也发生在舌头的味蕾中，该舌头被调整为“乌米米风味” - l-氨基酸的味道。该项目的总体目的是了解为什么tanycytes感应大脑中的氨基酸以及该信息的使用。我们的具体目的是：1。表征tanycytes检测并信号氨基酸浓度的机制； 2。确定氨基酸通过tanycytes是否与这些细胞中的其他营养感应方式相互作用 - 特别是它们感测葡萄糖的能力； 3。测试是否可以通过饮食（禁食，食物中的氨基酸量）改变氨基酸传感的性能； 4.检查氨基酸通过丹尼西群的贡献对确定食物偏好，食物摄入量以及最终控制体重的贡献。理解这种新的氨基酸传感途径的机制和功能作用，对临床医生和相关卫生专业人员都有许多好处；商业组织；相关的医疗慈善机构；政府机构；和公众。商业公司可以使用我们的工作来开发新型的食物添加剂，以减少食欲或重新制定食物，从而促进饱腹感。鉴于我们的工作，临床医生，营养师和相关的医疗慈善机构，可能能够对各种患者的饮食和饮食方式进行修改，以促进健康的饮食和体重减轻。政府机构可能能够对食品工业的政策进行修改，并向公众提供建议，以促进健康的饮食。

项目成果

Opposing modulation of Cx26 gap junctions and hemichannels by CO2.

CO2 对 Cx26 间隙连接和半通道的反向调节。

• DOI: 10.1113/jp280747
• 发表时间: 2021
• 期刊: The Journal of physiology
• 作者: Nijjar S

A sweet taste receptor-dependent mechanism of glucosensing in hypothalamic tanycytes.

• DOI: 10.1002/glia.23125
• 发表时间: 2017-05
• 期刊: Glia
• 影响因子: 6.2
• 作者: Benford H;Bolborea M;Pollatzek E;Lossow K;Hermans-Borgmeyer I;Liu B;Meyerhof W;Kasparov S;Dale N
• 通讯作者: Dale N

Amino acid sensing in hypothalamic tanycytes via umami taste receptors.

• DOI: 10.1016/j.molmet.2017.08.015
• 发表时间: 2017-11
• 期刊: Molecular metabolism
• 影响因子: 8.1
• 作者: Lazutkaite G;Soldà A;Lossow K;Meyerhof W;Dale N
• 通讯作者: Dale N