HEИндивидуална стипендия2023–2024

Virobe · Immunometabolic regulation of the host response to viral infection in the context of obesity

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2023-01-01 → 2024-12-31
Финансиране от ЕС: 214 934 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Връзката между затлъстяването и вирусните инфекции се проучва чрез наблюдение на мазнините, глюкозата и имунните клетки при мишки. Това помага да се разбере как загубата на тъкани и натрупването на мазнини в черния дроб влияят върху здравето на организма.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Immunometabolic regulation of the host response to viral infection in the context of obesity

The overall objective of this project was to study mechanisms of infection-induced tissue wasting in the contexts of obesity. We set out these two objectives: Objective 1: Are profiles of cytokines, macrophages, and glucose homeostasis altered in obese mice during LCMV infection compared to lean mice? Objective 2: Does targeting cytokines, macrophages and glucose homeostasis during LCMV infection impact on the progressive tissue wasting in obese mice, and do these factors crosstalk? New aspects in the project: we implemented a new angle/hypothesis to the study and investigated the consequences of the depleted adipose tissue on liver health. Circulating lipids can be deposited ectopically, and cause lipotoxicity and resultant insulin resistance and cardiometabolic dysfunctions. The major sink for lipids is the liver, and we studied liver pathology and systemic parameters associated with liver damage.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Chronic viral diseases are of significant concern to the public health due to lack of effective vaccines and paucity of potent anti-viral medication. Notably, individuals with obesity exhibit higher morbidity and mortality due to viral diseases. However, what specific mechanisms underlie the confounding effects of obesity on the overt outcome of viral infections remains poorly understood. In pre-clinical studies, I found that obese mice developed profound and progressive loss of fat and muscle in response to chronic viral infection, while metabolically healthy animals showed only transient and significantly milder manifestation of tissue wasting in response to the virus. In this proposal, I aim to identify the mechanisms driving this marked and progressive tissue wasting in infected obese mice. Inflammation and disrupted glucose homeostasis have been implicated to play a role in tissue wasting. I hypothesize that the profound tissue wasting during viral infection results from uncontrolled glucose homeostasis, perturbations in macrophage functions and from abnormal cytokine profiles observed in the context of obesity. I will test my hypothesis using high-fat diet-induced mouse model of obesity infected with chronic strain of the lymphocytic choriomeningitis virus. I will test the involvement of cytokines, macrophages as well as of glucose homeostasis in the progressive wasting in infected obese animals and evaluate if there is a crosstalk between these three factors during infection in an obese host. This project will generate critical knowledge to address why host response to virus is disrupted in the context of obesity and identify potential therapeutic strategies for improving the outcome of viral diseases such as tissue wasting in this metabolic disease. Moreover, this study will highlight the crosstalk between the immune system and body metabolism during infection and will help to better understand the processes underlying immunity to pathogens.

Оригинален текст от CORDIS (на английски).

Участници

KOBENHAVNS UNIVERSITET · KOBENHAVNКоординаторДания