Projektbeschreibung
Darmmikroben bekämpfen Stoffwechselerkrankungen
Adipositas und damit in Verbindung gebrachte Erkrankungen wie zum Beispiel Typ-2-Diabetes entwickeln sich gerade zu globalen Epidemien. Der Zusammenhang zwischen diesen Krankheiten und den Mikroben im menschlichen Darm (Mikrobiota) wird immer deutlicher, aber seine Mechanismen sind noch nicht ausreichend erforscht. Das EU-finanzierte Projekt Healthybiota untersucht nun mithilfe von Hightech-Methoden die Rolle der Darmmikrobiota bei der Regulierung des braunen Fetts. Im Gegensatz zum normalen weißen Fett ist das braune Fett ein echtes Kraftwerk des Stoffwechselgeschehens. Vollgepackt mit Mitochondrien und stark angeregt durch das sympathische Nervensystem, wandelt es chemische Energie über eine ohne Zittern funktionierende Thermogenese in Wärme um. Das Team möchte unter Einsatz von Mausmodellen und menschlichen Probanden Erkenntnisse über die Braunfettregulierung gewinnen, damit Behandlungen für Stoffwechselerkrankungen entwickelt werden können.
Ziel
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.
Wissenschaftliches Gebiet
- 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
Schlüsselbegriffe
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-COG - Consolidator GrantGastgebende Einrichtung
1211 Geneve
Schweiz