Exploring the effects of time-restricted feeding on the immune function of obese individuals: a multi-omic approach

探索限时喂养对肥胖个体免疫功能的影响：多组学方法

• 批准号: MR/X031381/1
• 负责人: Adil Mardinoglu
• 金额: $ 33.08万
• 依托单位: King's College London
• 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=MR%2FX031381%2F1
• 关键词: Exploring; effects; time; restricted; feeding

Pathological conditions associated with unbalanced nutrient handling, such as obesity, are associated with maladapted immune responses that lead to increased susceptibility to pathogenic infections. The precise mechanisms by which the immune system of obese subjects fails to adequately respond to pathogens remain unclear, but the adipose low-grade chronic inflammation that accompanies the obese condition seems to play a relevant role. Remarkably, dietary interventions based on severe caloric restriction have proven to exert beneficial effects on health, including the improvement of the immune function. However, chronic calorie restriction-based interventions usually fail due to poor adherence, highlighting the need for alternative nutritional interventions more appealing to patients but equally effective in terms of health benefits. Despite evidence supporting the effectiveness of time-restricted feeding (TRF) diets on the metabolic fitness of obese individuals, their impact on the immune function remains unexplored. On the view of the interplay observed between obesity, nutrition and immune function that outlines the host response to pathogens, the main goal of the OBESIMM project is to precisely define the effect that TRF exerts on the immune function of human obese individuals and how it impacts their immunocompetence. For this, we will conduct an interventional study in obese human individuals who will be subjected to a TRF diet and explore how this intervention reprograms their immune system to enhance their capacity to defend from infectious pathogens. We will use a multidisciplinary approach that combines cytomics, transcriptomics, metabolomics, metagenomics and systems biology, in order to unravel potential mechanisms involved in the modulation of immunity and theimprovement of adipose meta-inflammation by TRF. Our study in humans will be complemented with the use of preclinical models of obesity to directly assess the impact that TRF has on host's response to lipopolysaccharide. In addition, in line with the emerging use of nutraceuticals as complementary strategies to improve healthy habits and boost immune system, the preclinical model of obesity will be used also to study the effects of a multi-ingredient based on high soluble and bioavailable co-crystals ofthree bioactive compounds with immunomodulatory properties (pterostilbene, B-sitosterol and ubiquinol) on the host's response.

与肥胖症等营养不平衡处理相关的病理状况与免疫反应不良有关，从而导致对致病感染的敏感性增加。肥胖受试者免疫系统无法对病原体做出充分反应的确切机制尚不清楚，但是肥胖状况伴随的脂肪低度慢性炎症似乎起着相关作用。值得注意的是，基于严重热量限制的饮食干预措施已证明对健康产生有益的影响，包括改善免疫功能。但是，基于慢性卡路里的干预措施通常由于依从性差而失败，这突显了对替代营养干预措施的需求更具吸引力，但在健康益处方面同样有效。尽管有证据支持时间限制的喂养（TRF）饮食对肥胖个体的代谢适应性的有效性，但它们对免疫功能的影响仍未得到探索。根据概述宿主对病原体反应的肥胖，营养和免疫功能之间观察到的相互作用的观点，肥胖项目的主要目标是精确定义TRF对人类肥胖个体免疫功能的影响，以及它如何影响其免疫能力。为此，我们将对肥胖的人类进行介入研究，这些研究将接受TRF饮食，并探讨这种干预如何重新编程其免疫系统以增强其防御感染性病原体的能力。我们将使用一种多学科方法，该方法结合了细胞学学，转录组学，代谢组学，宏基因组学和系统生物学，以阐明参与免疫调节的潜在机制，并通过TRF促进脂肪荟萃炎症。我们在人类的研究将与使用肥胖的临床前模型直接评估TRF对宿主对脂多糖的反应的影响。此外，与新兴营养素作为改善健康习惯和增强免疫系统的互补策略一致，肥胖的临床前模型还将用于研究基于高可溶性和生物助剂的多型效果的效果主人的回应。