Description du projet
Les microbes intestinaux pourraient nous aider à lutter contre les troubles métaboliques
L’obésité et les troubles connexes comme le diabète de type 2 deviennent des épidémies mondiales. Le lien entre ces maladies et les microbes présents dans l’intestin humain (microbiote) est de plus en plus établi, mais les mécanismes ne sont pas bien compris. Le projet Healthybiota, financé par l’UE, recourt à des méthodes de haute technologie pour examiner le rôle du microbiote intestinal dans la régulation du tissu adipeux brun. Contrairement au tissu adipeux blanc courant, le tissu adipeux brun est une centrale métabolique. Doté de mitochondries et abondamment innervé par le système nerveux sympathique, il transforme l’énergie chimique en chaleur via une thermogenèse sans frisson. Recourant à des modèles murins et des sujets humains, l’équipe espère mieux comprendre la régulation du tissu adipeux brun, afin de développer des traitements pour les troubles métaboliques.
Objectif
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.
Champ scientifique
- 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
Mots‑clés
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
1211 Geneve
Suisse