Cytokine signalling, nutrition, longevity, and muscle health

细胞因子信号传导、营养、长寿和肌肉健康

• 批准号: BB/P000592/1
• 负责人: Marc Dionne
• 金额: $ 54.81万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FP000592%2F1
• 关键词: Cytokine; signalling; nutrition; longevity; muscle

In humans and other animals, nutrition has strong and complex effects on biology. Diets with different amounts of sugar, fat or protein can have important effects on physiology, even in the absence of obesity or obvious malnutrition; for example, it was reported last year that people who eat diets high in protein tend to die younger than others. In many cases, the effects of diet on physiology work by mechanisms that are not clear. We have begun to analyse this problem in fruit-flies; the advantage of doing this work in flies is that we can test the effects of many aspects of nutrition very quickly and relatively inexpensively. Many of the mechanisms of physiological regulation are conserved between flies and people.In our preliminary data, we show that in fruit-flies, macrophages - cells of the immune system - are a critical part of the nutrient sensing system. Macrophages appear to detect dietary protein and produce a signal that is received by muscles; this signal causes muscles to become less responsive to insulin. The signal from macrophages to muscles is critically important in allowing flies to live a normal lifespan and to be able to survive on diets that are low in sugar.The experiments we propose here have two parts. In the first part, we test the biological role in the macrophage of a pathway known to be responsive to dietary protein. In the second part, we use a variety of approaches to explore the signalling circuitry that connects macrophage sensing of diets with muscle physiology.Our preliminary results, combined with the proposed experiments, represent a dramatic step in our knowledge of how the body senses and responds to dietary components. This is a fundamentally new role for macrophages in normal physiology and reveals an entirely new way that dietary protein can affect lifespan and muscle physiology. Our work will have significant implications regarding age-related disease, inflammatory disease, and nutritional physiology.

在人类和其他动物中，营养对生物学有着强大而复杂的影响。即使没有肥胖或明显的营养不良，含有不同数量的糖、脂肪或蛋白质的饮食也会对生理产生重要影响;例如，去年有报道称，吃高蛋白质饮食的人往往比其他人死得更早。在许多情况下，饮食对生理的影响是通过尚不清楚的机制起作用的。我们已经开始在果蝇中分析这个问题;在果蝇中做这项工作的好处是，我们可以非常迅速地和相对便宜地测试营养的许多方面的影响。许多生理调节机制在果蝇和人类之间是保守的。在我们的初步数据中，我们表明，在果蝇中，巨噬细胞-免疫系统的细胞-是营养感应系统的关键部分。巨噬细胞似乎检测到饮食中的蛋白质，并产生一个被肌肉接收的信号;这个信号导致肌肉对胰岛素的反应降低。从巨噬细胞到肌肉的信号对于让苍蝇过上正常的寿命和能够在低糖饮食中生存至关重要。我们在这里提出的实验有两个部分。在第一部分中，我们测试了已知对膳食蛋白质有反应的途径在巨噬细胞中的生物学作用。在第二部分中，我们使用各种方法来探索连接巨噬细胞对饮食的感知与肌肉生理学的信号通路。我们的初步结果，结合拟议的实验，代表了我们在了解身体如何感知和响应饮食成分方面迈出的戏剧性一步。这是巨噬细胞在正常生理学中的一个全新作用，揭示了膳食蛋白质影响寿命和肌肉生理学的一种全新方式。我们的工作将对年龄相关疾病、炎症性疾病和营养生理学产生重要影响。

项目成果

fs(1)h controls metabolic and immune function and enhances survival via AKT and FOXO in Drosophila.

fs(1)h 在果蝇中通过 AKT 和 FOXO 控制代谢和免疫功能并提高存活率。

• DOI: 10.1242/dmm.037259
• 发表时间: 2019
• 期刊: Disease models & mechanisms
• 影响因子: 4.3
• 作者: Sharrock J

Origins of Metabolic Pathology in Francisella-Infected Drosophila.

弗朗西斯菌感染的果蝇代谢病理学的起源。

• DOI: 10.3389/fimmu.2020.01419
• 发表时间: 2020
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Vincent CM

A serine-folate metabolic unit controls resistance and tolerance of infection

丝氨酸-叶酸代谢单位控制感染的抵抗力和耐受性

• DOI: 10.1101/2022.11.25.517956
• 发表时间: 2022
• 作者: Grimes K

Infection increases activity via Toll dependent and independent mechanisms in Drosophila melanogaster.

• DOI: 10.1371/journal.ppat.1010826
• 发表时间: 2022-09
• 期刊: PLoS pathogens
• 影响因子: 6.7

Muscle function and homeostasis require macrophage-derived cytokine inhibition of AKT activity in Drosophila

果蝇的肌肉功能和体内平衡需要巨噬细胞衍生的细胞因子抑制 AKT 活性

• DOI: 10.1101/763557
• 发表时间: 2019
• 作者: Kierdorf K