Mechanistic regulation of systemic bone and inflammatory responses to exercise and feeding in humans

运动和进食会引发人类循环骨和炎症生物标记物以及免疫细胞的暂时变化。这些反应也可以通过体内脂肪水平的增加(肥胖)来改变，因为脂肪组织分泌的促炎分子可能对这些生理反应进行不同的调节。我以前的工作表明，一次运动可以诱导骨骼和炎症生物标记物反应。然而，关于摄取不同的食物/营养物质如何影响运动的急性骨骼和炎症生物标记物反应，这些过程(骨代谢和炎症)如何相互影响，以及肥胖症如何调节这些相互作用，人们知之甚少。此外，评估循环免疫细胞的功能和免疫细胞在暴露于这些临时应激源/调节剂后产生的炎症分子将进一步加深我们对这些过程的机械理解。考虑到知识的差距，我的研究计划的目的是调查运动和喂养如何改善正常和改变(即肥胖增加)的人类新陈代谢模型中的骨代谢和炎症。在接下来的5年里，我将在急性运动后测试不同的乳制品及其营养成分作为营养调节剂。乳制品(如牛奶和希腊酸奶[GY])含有直接影响骨骼新陈代谢的营养物质，并含有影响炎症的抗氧化剂/抗炎生物活性。这使得它们和它们的组成营养物质适合的喂养模式，以更好地理解这些生理反应/关系。9名受训者(2名硕士、2名博士、5名本科生)将(与现有的基础设施和专家合作者一起)开展6个新项目，回答有关骨骼/炎症生物标志物和免疫细胞如何通过运动后差异化喂养对一轮运动做出反应的针对性问题。此外，使用创新的机械技术，我们将评估有/没有次级细菌触发的主要触发因素(运动/喂养)如何影响急性免疫细胞功能。实验的特点是高冲击/负荷运动，然后用牛奶、GY、碳水化合物、蛋白质、钙或水喂养。血液样本将在基线和运动后48小时以上采集。一些补充剂将在体内脂肪水平增加的人类身上进行测试，以评估在不同的生理/炎症环境中的反应。来自这个DG的资金将促进基础研究的全面收集，这些基础研究将产生基础知识，并促进我们对运动和喂养对人体骨骼新陈代谢和炎症反应和机制的影响的理解。结果还将产生适用于不同最终用户的知识，侧重于在不同情况下的急性运动恢复和慢性运动训练的营养优化，并将有力地应用于食品科学/补充剂行业，为创新产品配方提供信息。

Exercise and feeding trigger temporary changes in circulating bone and inflammatory biomarkers, and immune cells in humans. These responses can also be altered by increased levels of body fat (adiposity) since fat tissue secretes pro-inflammatory molecules that may differentially regulate these physiological responses. My previous work demonstrated that one bout of exercise induces bone and inflammatory biomarker responses. However, little is known about how feeding different foods/nutrients affect acute bone and inflammatory biomarker responses to exercise, how these processes (bone metabolism and inflammation) influence each other, and how adiposity mediates these interactions. Moreover, assessing circulating immune cell function and the inflammatory molecules immune cells produce after exposure to these temporary stressors/modulators will further add to our mechanistic understanding of these processes. Given the knowledge gaps, the aim of my research program is to investigate how exercise and feeding modify bone metabolism and inflammation in normal and altered (i.e., increased adiposity) human models of metabolism. Over the next 5 years, I will test different dairy foods and their constituent nutrients post acute exercise as nutritional modulators. Dairy foods (i.e., milk and Greek yogurt [GY]) contain nutrients that directly affect bone metabolism and have antioxidant/anti-inflammatory bioactives affecting inflammation. This makes them and their constituent nutrients appropriate feeding models to better understand these physiological responses/relationships. Nine trainees (2 MSc, 2 PhD, 5 undergraduate) will undertake 6 novel projects (with existing infrastructure and expert collaborators) to answer targeted questions on how bone/inflammatory biomarkers and immune cells respond to one bout of exercise for up to 48h with differential post-exercise feeding. Further, using innovative mechanistic techniques, we will assess how the primary triggers (exercise/feeding) with/without a secondary bacterial trigger affects acute immune cell function. Experiments feature high impact/load exercise followed by feeding with either milk, GY, carbohydrate, protein, calcium, or water. Blood samples will be taken at baseline and over 48h post-exercise. Some supplements will be tested in humans with increased body fat levels to assess these responses in a different physiological/inflammatory environment. Funds from this DG will facilitate a comprehensive collection of basic research that will generate fundamental knowledge and advance our understanding of the effects of exercise and feeding on responses and mechanisms of human bone metabolism and inflammation. Results will also generate knowledge applicable to diverse end-users focused on the nutritional optimization of acute exercise recovery and chronic exercise training in different contexts and has strong application to the food science/supplement industries informing innovative product formulations.