Decoding interactions between adipose tissue immune cells, metabolic function, and the intestinal microbiome in obesity

Informazioni relative al progetto

ADIMMUNE

ID dell’accordo di sovvenzione: 819439

DOI

10.3030/819439

Progetto chiuso

Data della firma CE 20 Febbraio 2019

Data di avvio 1 Marzo 2019

Data di completamento 29 Febbraio 2024

Finanziato da

• EXCELLENT SCIENCE - European Research Council (ERC)

Costo totale

€ 2 000 000,00

Contributo UE

€ 2 000 000,00

Coordinato da

WEIZMANN INSTITUTE OF SCIENCE
Israel

Periodic Reporting for period 4 - ADIMMUNE (Decoding interactions between adipose tissue immune cells, metabolic function, and theintestinal microbiome in obesity)

Periodo di rendicontazione: 2023-09-01 al 2024-02-29

Sintesi del contesto e degli obiettivi generali del progetto

Obesity constitutes a global epidemic, leading to widespread metabolic complications, such as type 2 diabetes mellitus and cardiovascular diseases. Yet, the mechanisms leading to obesity-associated metabolic complications remain obscure. Fat (adipose) tissue inflammation and inflammatory signals derived from both immune cells and fat cells significantly impact metabolic disorders associated with obesity. In addition the gut bacteria directly influence metabolic disease progression.
The problem/issue being addressed: What are the adipose immune signals and their cross-talk with the gut bacteria impacting the development of metabolic syndrome disorders?
The importance of this study to the society: this study can potentially identify therapeutic targets for treating obesity and its associated metabolic disorders such as insulin resistance and type 2 diabetes.
The overall objectives of this study were: (1) To investigate the unique immune cell populations and signals emerging in response to obesity and to study their impact on development and progression of metabolic complications. (2) To reveal the cross-talk between adipose immune cells and the gut microbiota and their involvement in obesity and metabolic disorders

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

In this study, we discovered a novel adipose immune cell population that is uniquely generated only as a response to obesity in both humans and mice. This unique immune cell population has a role in lipid uptake and storage in obesity. Next, we deleted in mice a lipid receptor specifically expressed in the unique immune population and the resulting mice had aggravated weight gain and metabolic disorders indicating its central role in the development of obesity and metabolic complications. In addition to fat, we used the technology developed in our study to explore other immune and non-immune cells involved in other organs in other diseases such acute liver failure and lung viral infection such as flu.
Next, we discovered the connection between gut microbiome-derived metabolites and the immune population in the fat tissues. We found that one of these metabolites induce obesity and metabolic syndrome disorders leading to aggravated inflammation in the fat tissues, whereas the other one caused an opposite impact leading to prevention of obesity and reduction in metabolic diseases and fat inflammation.
Exploitation and dissemination: results of this project have been already integrated into several stories published in world-leading peer-reviewed journals, and presented in over 100 plenary talks and symposia. In addition, I’m engaged in continuous dissemination activity of these results in the form of media interviews, and laymen talks.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

Using an innovative genomics technique, we discovered a new population of immune cell in fat tissues that act as a lipid buffering system from the environment, which is crucial for dealing with obesity and metabolic diseases. Using similar method, we identified a special population of liver cells involves in acute live failure, and in another study, we discovered lung immune cells that are modified in diabetes and weakening the lung’s response to viral infections such as flu and COVID-19.
In another study we discovered metabolites derived from the gut microbiome that can influence weigh gain as results of smoking cessation. We further expanded these findings into non-smoking conditions and found that these metabolites impact the development of obesity, metabolic diseases and fat inflammation. This suggests they could be promising interventions for managing obesity in humans.

figure-for-publication-lams-and-scwg.png