Project description
Investigating the crosstalk between adipose tissue and intestinal microbiome in obesity
Obesity is a global medical issue and a risk factor for metabolic diseases such as diabetes. Emerging evidence indicates that adipose tissue undergoes changes in obesity and may display inflammatory features. The EU-funded ADIMMUNE project is interested to understand the role of the gut microbiome and metabolites in obesity. Researchers will focus on the immune cells found in white adipose tissue and the way they integrate external signals to maintain metabolic homeostasis. Results will provide fundamental insight into the underlying aetiology of obesity complications and pave the way towards novel therapeutic interventions.
Objective
Obesity and its metabolic co-morbidities have given rise to a rapidly expanding ‘metabolic syndrome’ pandemic affecting
hundreds of millions of individuals worldwide. The integrative genetic and environmental causes of the obesity pandemic
remain elusive. White adipose tissue (WAT)-resident immune cells have recently been highlighted as important factors
contributing to metabolic complications. However, a comprehensive understanding of the regulatory circuits governing their
function and the cell type-specific mechanisms by which they contribute to the development of metabolic syndrome is
lacking. Likewise, the gut microbiome has been suggested as a critical regulator of obesity, but the bacterial species and
metabolites that influence WAT inflammation are entirely unknown.
We propose to use our recently developed high-throughput genomic and gnotobiotic tools, integrated with CRISPR-mediated interrogation of gene function, microbial culturomics, and in-vivo metabolic analysis in newly generated mouse models, in order to achieve a new level of molecular understanding of how WAT immune cells integrate environmental cues into their crosstalk with organismal metabolism, and to explore the microbial contributions to the molecular etiology of WAT inflammation in the pathogenesis of diet-induced obesity. Specifically, we aim to (a) decipher the global regulatory landscape and interaction networks of WAT hematopoietic cells at the single-cell level, (b) identify new mediators of WAT immune cell contributions to metabolic homeostasis, and (c) decode how host-microbiome communication shapes the development of WAT inflammation and obesity.
Unraveling the principles of WAT immune cell regulation and their amenability to change by host-microbiota interactions
may lead to a conceptual leap forward in our understanding of metabolic physiology and disease. Concomitantly, it may
generate a platform for microbiome-based personalized therapy against obesity and its complications.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- medical and health scienceshealth sciencespublic healthepidemiologypandemics
- medical and health sciencesbasic medicineimmunology
- natural sciencesbiological sciencesmicrobiology
- medical and health sciencesbasic medicinephysiologyhomeostasis
- medical and health scienceshealth sciencesnutritionobesity
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Keywords
Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
7610001 Rehovot
Israel