Elucidating the impact of the microbiome on adipose tissue immune cell interactions during obesity

ended

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.