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

Informations projet

ADIMMUNE

N° de convention de subvention: 819439

DOI

10.3030/819439

Projet clôturé

Date de signature de la CE 20 Février 2019

Date de début 1 Mars 2019

Date de fin 29 Février 2024

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 2 000 000,00

Contribution de l’UE

€ 2 000 000,00

Coordonné par

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)

Période du rapport: 2023-09-01 au 2024-02-29

Résumé du contexte et des objectifs généraux du projet

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

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

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.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

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.

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