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.

与营养处理不平衡相关的病理状况（例如肥胖）与适应不良的免疫反应有关，从而导致对病原体感染的易感性增加。肥胖受试者的免疫系统未能对病原体做出充分反应的确切机制尚不清楚，但伴随肥胖状况的脂肪低度慢性炎症似乎发挥了相关作用。值得注意的是，基于严格热量限制的饮食干预已被证明对健康产生有益影响，包括改善免疫功能。然而，基于长期热量限制的干预措施通常会因依从性差而失败，这凸显出需要对患者更有吸引力但在健康益处方面同样有效的替代营养干预措施。尽管有证据支持限时喂养（TRF）饮食对肥胖个体代谢健康的有效性，但它们对免疫功能的影响仍未得到探索。根据观察到的肥胖、营养和免疫功能之间的相互作用（概述了宿主对病原体的反应），OBESIMM 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他们的免疫能力。为此，我们将对接受 TRF 饮食的肥胖人群进行一项干预性研究，并探讨这种干预如何重新编程他们的免疫系统，以增强他们防御传染性病原体的能力。我们将采用结合细胞组学、转录组学、代谢组学、宏基因组学和系统生物学的多学科方法，以揭示 TRF 调节免疫和改善脂肪元炎症的潜在机制。我们对人类的研究将通过使用临床前肥胖模型来补充，以直接评估 TRF 对宿主对脂多糖反应的影响。此外，随着营养保健品作为改善健康习惯和增强免疫系统的补充策略的兴起，肥胖的临床前模型也将用于研究基于高可溶性和生物利用度共晶的多种成分的效果三种具有免疫调节特性的生物活性化合物（紫檀芪、B-谷甾醇和泛醇）对宿主反应的影响。