Descrizione del progetto
Il microbioma e le interazioni cellulari nell’obesità
Il tessuto adiposo bianco è il principale deposito di energia e svolge un ruolo chiave nell’omeostasi energetica. Gli adipociti regolano il metabolismo e l’insulino-resistenza rilevando la domanda di energia e secernendo i fattori paracrini. Nell’obesità il tessuto adiposo bianco può essere disfunzionale e non riuscire a soddisfare l’eccesso di energia. L’ipotesi su cui lavora il progetto INTERFAT, finanziato dall’UE, è che l’obesità sia una malattia multifattoriale in cui l’interazione degli adipociti con le cellule immunitarie e il microbiota intestinale svolgerebbero ruoli di primaria importanza. I ricercatori approfondiranno le interazioni cellulari e le ripercussioni dei batteri commensali dell’intestino sull’obesità indotta da una dieta ad alto contenuto di grassi. I risultati faranno progredire le nostre conoscenze in merito alla biologia degli adipociti e sveleranno nuovi meccanismi coinvolti nell’obesità.
Obiettivo
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.
Campo scientifico
- natural sciencesbiological sciencesmicrobiologybacteriology
- medical and health scienceshealth sciencespublic healthepidemiologypandemics
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesclinical medicinetransplantation
- medical and health scienceshealth sciencesnutritionobesity
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF-EF-ST - Standard EFCoordinatore
7610001 Rehovot
Israele