Project description
Gut microbes may help us fight metabolic disorders
Obesity and related disorders such as type 2 diabetes are becoming global epidemics. The link between these diseases and microbes in the human gut (microbiota) is increasingly clear but the mechanisms are not well understood. The EU-funded Healthybiota project is using high-tech methods to investigate the role of gut microbiota in brown fat regulation. Unlike common white fat, brown fat is a metabolic powerhouse. Packed with mitochondria and heavily innervated by the sympathetic nervous system, it turns chemical energy into heat via non-shivering thermogenesis. Using mouse models and human subjects, the team hopes to gain insight into brown fat regulation to develop treatments for metabolic disorders.
Objective
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.
Fields of science
- 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
Keywords
Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
1211 Geneve
Switzerland