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.

近三分之二的英国人口超重或肥胖。这种超重会增加过早死亡和一系列疾病的风险，如糖尿病和中风，大大降低生活质量。下丘脑在基地的大脑控制体重通过调节食物摄入量（虽然感觉饥饿和饱腹感），也沉积脂肪和支出的能量（作为热量的生产和活动）。了解大脑如何发出饥饿和饱腹的信号是我们开始制定减少人群超重发生率的策略的一种方式。食物中的氨基酸含量是饱腹感的一个强有力的决定因素。当血浆中的氨基酸水平很高时，饱腹感也很强。氨基酸在大脑中被检测到。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做出反应。我们建议研究第五种机制，这是独特的，因为它不是由神经细胞介导的，而是由下丘脑中称为tanycells的专门的神经胶质细胞介导的。我们已经表明，伸长细胞对氨基酸有反应，这可能是通过激活舌头味蕾中的一种受体来实现的，这种受体也被调谐到“鲜味”--L-氨基酸的味道。本研究的主要目的是了解为什么大脑中的伸长细胞能感知氨基酸，以及这些信息的用途。表征伸长细胞检测和信号氨基酸浓度的机制; 2.确定通过伸长细胞的氨基酸感测是否与这些细胞中的其他营养感测方式相互作用-特别是它们感测葡萄糖的能力; 3.测试饮食（禁食、食物中的氨基酸含量）是否可以改变通过伸展细胞传感氨基酸的特性; 4.研究通过伸长细胞的氨基酸传感对确定食物偏好、食物摄入量和最终控制体重的贡献。了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、商业组织、相关医疗慈善机构、政府机构和公众都有很多好处。商业公司可能会利用我们的工作来开发新型的食品添加剂，减少食欲，或重新配制食品，使其促进饱腹感。根据我们的工作，临床医生，营养师和相关的医疗慈善机构可能能够修改对不同类别患者的饮食和饮食模式的建议，以促进健康饮食和减肥。政府机构可能能够修改其有关食品工业的政策，并向公众提供促进健康饮食的建议。

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