Descrizione del progetto
I microbi intestinali possono aiutarci a combattere i disturbi metabolici
L’obesità e i disturbi correlati quali il diabete di tipo 2 stanno diventando epidemie globali. Il collegamento tra queste malattie e i microbi nell’intestino umano (microbiota) è sempre più chiaro ma i meccanismi non sono ben compresi. Il progetto Healthybiota, finanziato dall’UE, sta utilizzando metodi ad alta tecnologia per studiare il ruolo del microbiota intestinale nella regolazione del grasso bruno. A differenza del grasso bianco comune, il grasso bruno è una centrale metabolica. Ricco di mitocondri e fortemente innervato dal sistema nervoso simpatico, esso trasforma l’energia chimica in calore mediante la termogenesi senza brivido. Utilizzando modelli murini e soggetti umani, il team spera di ottenere informazioni sulla regolazione del grasso bruno per sviluppare trattamenti per i disordini metabolici.
Obiettivo
Obesity is a metabolic disorder leading to various health risks and reduced life expectancy. Insulin resistance is a major obesity related disorder, and a main cause for the onset of type 2 diabetes. During cold exposure or caloric restriction (CR), brown adipocytes emerge within the white fat (known as “beige” cells). This process, referred to as fat browning, increases the metabolic capacity of the adipose tissues to combust energy and is seen as promising anti-obesity and anti-diabetic strategy. The intestinal microbiota co-develops with the host; microbiota depletion, or cold-induced shift of its composition are sufficient to improve insulin sensitivity and glucose metabolism, in part mediated by the innate immune system-mediated fat browning. The microbial signals and composition, critical for our understanding of the microbiota-host mutualism and metabolic improvements during cold and CR, remain unclear.
By integrating expertise from several areas including physiology, bioinformatics, immunology, microbiology and developmental biology; and by developing computational approaches for comparing the metagenomics, metabolomics and transcriptomics data from the CR- and the cold-exposed mice with cohorts of human subjects, we will establish the microbiota role in orchestrating the CR-induced metabolic improvements and innate immune response, and provide mechanistic explanations on the microbiota-host mutualism during CR and cold. Finally, by using lineage-tracing studies and developing transgenic mouse models, we will determine the importance of the beige fat in the CR-induced beneficial effects on the host, and the importance of the microbiota in mediating this process. Manipulating the gut microbiota and exploiting the mechanistic links revealed by this study would be of conceptual importance for our understanding of microbiota-host mutualism in the metabolic homeostasis, and could lead to development of novel therapeutics for improving metabolic health.
Campo scientifico
- medical and health sciencesclinical medicineendocrinologydiabetes
- medical and health sciencesbasic medicineimmunology
- natural sciencesbiological sciencesbiological behavioural sciencesethologybiological interactions
- medical and health sciencesbasic medicinephysiologyhomeostasis
- medical and health scienceshealth sciencesnutritionobesity
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
1211 Geneve
Svizzera