INTERFAT · Elucidating the impact of the microbiome on adipose tissue immune cell interactions during obesity
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-06-01 → 2021-05-31
- EU contribution
- €173,464
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Elucidating the impact of the microbiome on adipose tissue immune cell interactions during obesity
Why do we need to further the study on adipose tissue? Because it lays the foundation for research into an unprecedented dilemma we are facing right now: For the first time in the history of human kind, the number of people affected by overnutrition now exceeds the number of those suffering from malnutrition. The obesity pandemic represents a major burden to public health and to the socio-economic system globally. Given the current data provided by the World Health Organization, the prevalence of overweight among adults worldwide is 39% for both sexes, and 18% among children and adolescents. In the EU according to eurostat, at 51.6%, the majority of people over 18 years of age are overweight. These numbers indicate that overall preventive and therapeutic measures have failed. One reason might be the lack of understanding of adipose tissue biology, which is implicated in fundamental physiological processes and in pathophysiological developments. The problem is a lack of comprehensive understanding of the systemic aspects of adipose tissue and the consequences of its deterioration during obesity for our society as a whole. The environment and our social behaviour shape our dietary habits, sleeping and activity patterns, and stress exposure. Such factors serve as “input” cues to our physiology in general and to adipose tissue as a metabolic hub of our body in particular. The tissue generates “output”, because it serves as an endocrine organ secreting different hormones, and it forms a niche populated by immune cells. Therefore, the overall objectives of InterFat were I) systematically characterize populations of murine adipocytes and adipose tissue immune cells at the steady state and during obesity and II) profile the impact of the intestinal microbiome on adipose tissue composition and function. The microbiome is an important sensor of “input” cues as it is strongly depending on environmental factors such as nutrition and life style.
Data: CORDIS, © European Union
Project objective
Obesity affects hundreds of millions of people worldwide and poses a major burden on global health and economy. Immune cells residing in white adipose tissue (WAT) have recently been highlighted as important factors contributing to metabolic dysfunctions during obesity, which is characterized by chronic low-grade inflammation of fat depots. The yet unresolved interplay between adipocytes and immune cells in the WAT niche represents a major challenge to any rational interference into the metabolic derailments. Likewise, the microbiome has been suggested as a critical mediator of obesity, but the regulatory mechanisms remain elusive.My project aims at a comprehensive assessment of the adipocytes, the adipose tissue immune cells, and their intercellular communication circuits during high-fat diet-induced obesity, as well as the exploration of the impact of the intestinal microbiota on this dynamic process. First, I will characterize adipocytes and immune cells in WAT at the steady state and during obesity of mice by means of single-nuclei RNA-sequencing. Then, I will utilise these transcriptomic profiles for computational modelling to discover disease-specific cell-to-cell interactions, and validate them in signal transduction experiments. This approach together with the analysis of faecal microbiome transplantations into germ-free mice will define the contribution of intestinal microbiota to the WAT remodelling during obesity. By elucidating the impact of commensal bacteria on adipose tissue cell-to-cell interaction networks, my project aims to take a radically new approach in studying the microbiome-adipose tissue axis and its mechanistic contribution to the aetiology of the obesity pandemic. This systems biology approach may lead to a conceptual leap forward in our understanding of adipocyte biology and WAT immune cell regulation, thereby exploring possibilities for microbiome-based personalized therapies against adipose tissue inflammation during obesity.
Original text from CORDIS.
Participants
- WEIZMANN INSTITUTE OF SCIENCE · RehovotCoordinatorIsrael
Links
Data: CORDIS, © European Union