A platform to investigate multi-tissue crosstalk mediated by exercise induced soluble factors released from human skeletal muscle

研究运动诱导的人体骨骼肌释放的可溶性因子介导的多组织串扰的平台

• 批准号: NC/X001970/1
• 负责人: Mark Lewis
• 金额: $ 25.63万
• 依托单位: Loughborough University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=NC%2FX001970%2F1
• 关键词: platform; investigate; multi; tissue; crosstalk

The benefits of exercise are well documented, whereby people regularly undertaking some form of physical activity score highly in measures of fitness, health and mental wellbeing. Exercise is also known to reduce the likelihood of developing a number of diseases including (but not limited to): type 2 diabetes, dementia and cancer. Participation in exercise does not cause severe side effects, and in many cases is considered as effective as some prescribed medical interventions in the cure and reduction of symptoms. However, despite these clear advantages, exercise is rarely used as a clinical intervention. One reason for its infrequent use is that individuals respond differently to the same exercise intervention, with some people not responding at all. Additionally, a specific exercise intervention may improve one health outcome but not another, an effect that is increasingly variable between patients. This makes exercise prescription challenging. To overcome this, we need new methods of determining whether exercise interventions are effective for the specific organ/tissue (e.g. liver or muscle) being targeted, and whether each unique patient is responsive to that mode of treatment. As skeletal muscle adapts to exercise it also communicates with other organs and tissues both directly (e.g. bone) and indirectly (e.g. pancreas). This phenomenon is termed crosstalk. Our current understanding of this crosstalk is that biological materials (named exerkines) are released as we exercise and are able to travel between tissue/organs. Latest studies suggest that this crosstalk may be responsible for many of the health benefits associated with exercise. These current studies have been conducted in both humans and animals during exercise. However, the biological complexity of animals and humans makes it difficult to model crosstalk associated with a single tissue, as the rest of the bodily functions mask these signals. These studies are also expensive, time consuming, and in the case of animal modelling unethical. Therefore, we need new methods (not using humans/animals) that allow us to understand more about the role of exerkines, and determine their effect on other tissues. To achieve this, this research will: a) recreate protocols that mimic skeletal muscle during exercise within lab grown tissues, b) measure and monitor the exerkines produced during this exercise c) administer these exerkines to other tissues (e.g. bones) so we can understand how they affect different parts of the body. The long-term vision of this work is that we can reduce, and ultimately replace, the animal models currently used in this research, and provide a way of modelling tissue crosstalk that allows us to assess biological crosstalk in a level of detail in which existing models cannot.

运动的好处是有据可查的，人们经常进行某种形式的体育活动，在健身，健康和心理健康方面得分很高。运动也被认为可以降低发展许多疾病的可能性，包括（但不限于）：2型糖尿病，痴呆和癌症。参与运动不会引起严重的副作用，在许多情况下，在治疗和减轻症状方面，运动被认为与一些处方药物干预一样有效。然而，尽管有这些明显的优势，运动很少被用作临床干预。它不经常使用的一个原因是，个人对相同的运动干预的反应不同，有些人根本没有反应。此外，特定的运动干预可能会改善一种健康结果，但不会改善另一种健康结果，这种效果在患者之间的差异越来越大。这使得运动处方具有挑战性。为了克服这一点，我们需要新的方法来确定运动干预是否对靶向的特定器官/组织（例如肝脏或肌肉）有效，以及每个独特的患者是否对这种治疗模式有反应。当骨骼肌适应运动时，它也与其他器官和组织直接（例如骨骼）和间接（例如胰腺）沟通。这种现象称为串扰。我们目前对这种串扰的理解是，生物材料（称为exerkines）在我们运动时释放，并且能够在组织/器官之间旅行。最新的研究表明，这种串扰可能是与运动相关的许多健康益处的原因。目前的这些研究是在人类和动物运动期间进行的。然而，动物和人类的生物复杂性使得难以对与单个组织相关联的串扰进行建模，因为身体的其余功能掩盖了这些信号。这些研究也是昂贵的，耗时的，并且在动物模型的情况下是不道德的。因此，我们需要新的方法（不使用人类/动物），使我们能够更多地了解运动因子的作用，并确定它们对其他组织的影响。为了实现这一目标，本研究将：a）在实验室生长的组织中重建模拟骨骼肌运动的方案，B）测量和监测运动过程中产生的运动因子，c）将这些运动因子施用于其他组织（例如骨骼），以便我们能够了解它们如何影响身体的不同部位。这项工作的长期愿景是，我们可以减少并最终取代目前在这项研究中使用的动物模型，并提供一种建模组织串扰的方法，使我们能够在现有模型无法达到的细节水平上评估生物串扰。