Description du projet
Interactions entre le microbiome et les cellules dans l’obésité
La graisse blanche (GB) est le principal réservoir d’énergie et joue un rôle clé dans l’homéostasie énergétique. Les adipocytes régulent le métabolisme et la résistance à l’insuline en détectant les demandes énergétiques et en sécrétant des facteurs paracrines. En cas d’obésité, la GB peut être dysfonctionnelle et incapable de répondre à l’excès d’énergie. L’hypothèse de travail du projet INTERFAT, financé par l’UE, est que l’obésité est une maladie multifactorielle dans laquelle l’interaction des adipocytes avec les cellules immunitaires et le microbiote intestinal joue un rôle clé. Les chercheurs étudieront les interactions cellulaires et l’implication des bactéries intestinales commensales dans l’obésité induite par un régime riche en graisses. Les résultats feront progresser nos connaissances sur la biologie des adipocytes et dévoileront de nouveaux mécanismes de l’obésité.
Objectif
Obesity affects hundreds of millions of people worldwide and poses a major burden on global health and economy. Immune cells residing in white adipose tissue (WAT) have recently been highlighted as important factors contributing to metabolic dysfunctions during obesity, which is characterized by chronic low-grade inflammation of fat depots. The yet unresolved interplay between adipocytes and immune cells in the WAT niche represents a major challenge to any rational interference into the metabolic derailments. Likewise, the microbiome has been suggested as a critical mediator of obesity, but the regulatory mechanisms remain elusive.
My project aims at a comprehensive assessment of the adipocytes, the adipose tissue immune cells, and their intercellular communication circuits during high-fat diet-induced obesity, as well as the exploration of the impact of the intestinal microbiota on this dynamic process.
First, I will characterize adipocytes and immune cells in WAT at the steady state and during obesity of mice by means of single-nuclei RNA-sequencing. Then, I will utilise these transcriptomic profiles for computational modelling to discover disease-specific cell-to-cell interactions, and validate them in signal transduction experiments. This approach together with the analysis of faecal microbiome transplantations into germ-free mice will define the contribution of intestinal microbiota to the WAT remodelling during obesity.
By elucidating the impact of commensal bacteria on adipose tissue cell-to-cell interaction networks, my project aims to take a radically new approach in studying the microbiome-adipose tissue axis and its mechanistic contribution to the aetiology of the obesity pandemic. This systems biology approach may lead to a conceptual leap forward in our understanding of adipocyte biology and WAT immune cell regulation, thereby exploring possibilities for microbiome-based personalized therapies against adipose tissue inflammation during obesity.
Champ scientifique
- natural sciencesbiological sciencesmicrobiologybacteriology
- medical and health scienceshealth sciencespublic healthepidemiologypandemics
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesclinical medicinetransplantation
- medical and health scienceshealth sciencesnutritionobesity
Programme(s)
Régime de financement
MSCA-IF-EF-ST - Standard EFCoordinateur
7610001 Rehovot
Israël