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

Projektinformationen

Virobe

ID Finanzhilfevereinbarung: 101063888

DOI

10.3030/101063888

Projekt abgeschlossen

EK-Unterschriftsdatum 13 Juni 2022

Startdatum 1 Januar 2023

Enddatum 31 Dezember 2024

Finanziert unter

• Marie Skłodowska-Curie Actions (MSCA)

Gesamtkosten

Keine Daten

EU-Beitrag

€ 214 934,40

Koordiniert durch

KOBENHAVNS UNIVERSITET
Denmark

Periodic Reporting for period 1 - Virobe (Immunometabolic regulation of the host response to viral infection in the context of obesity)

Berichtszeitraum: 2023-01-01 bis 2024-12-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

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.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

The main scientific achievements encompass the following:

(i) I characterized the metabolic and immunological aspects of the host response to chronic viral infection in the settings of obesity; this can be further investigated by looking if various chronic inflammatory settings in obese subjects show similar pattern of response;
(ii) I identified CD8+ T cells as a potential target for limiting infection-induced fat wasting in obese population; this can be further investigated by assessing the role of these cells in other wasting conditions observed in obese population, e.g. cancer;
(iii) Identified negative consequences on the liver health during vast adipose tissue depletion in infection settings; this can be further investigated by assessing if these changes are transient or progressive, and by addressing the correlation of inflammation and MASLD in both obese and non-obese settings;
(iv) I rejected the hypothesis that the blockade of the pro-cachectic mediator TNF- and the blood glucose-lowering drug metformin could be used for treating infection-induced fat depletion;

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

With the MSCA project, we showed for the first time that chronic viral infection induces vast and progressive depletion of fat in obese animals. Such profound fat depletion can have negative consequences on the whole body because circulating fat derived from fat tissue can be deposited ectopically, and cause lipotoxicity fuelling insulin resistance and cardiometabolic complications. Several publications reported that chronic viral diseases in humans often correlate with higher liver steatosis, with limited insights into mechanisms driving this phenomenon. Here, we found a link between infection-induced fat depletion and lipid deposition in the liver. Our findings can be a base for investigation of the processes regulating the crosstalk between the adipose tissue and liver in the settings of infection. Finally, I view it highly important to raise awareness, that fat depletion is not always beneficial and it does depend on the conditions, e.g. in the settings of inflammation where fat depletion can be detrimental on liver health.