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

点击翻译按钮获取中文摘要

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.