Periodic Reporting for period 1 - INTERFAT (Elucidating the impact of the microbiome on adipose tissue immune cell interactions during obesity)
Berichtszeitraum: 2019-06-01 bis 2021-05-31
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.
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.
The results of InterFat include a successfully established protocol allowing the isolation of cytoplasmic and nuclear mRNA from the whole adipose tissue, including both, mature adipocytes as well as precursor cells and non-adipocytes. A comprehensive dataset has been generated comprising more than 50,000 transcriptomes from single cells and nuclei, respectively. The generated data represents a rich resource for the molecular characterization of mature adipocytes and their subsets contributing to the pathophysiology of adipose tissue. Differences in cell type composition and function within adipose tissue can now be systematically compared between the presence (i.e. in specific-pathogen-free mice) or absence (i.e. in germ-free mice) of intestinal bacteria.
These data can be exploited to identify cellular and molecular entities, which are involved in the remodelling of adipose tissue during the transition from the physiological state to the obese state for a rational intervention. We have exemplified this by genetic ablation of two molecules involved in lipid homeostasis and indeed find altered dynamics in weight gain, which warrants further studies. Results have been disseminated at international conferences as well as online seminars and helped me to secure a position as an independent junior group leader. The InterFat data will serve as foundation for my future research endeavours.
These data can be exploited to identify cellular and molecular entities, which are involved in the remodelling of adipose tissue during the transition from the physiological state to the obese state for a rational intervention. We have exemplified this by genetic ablation of two molecules involved in lipid homeostasis and indeed find altered dynamics in weight gain, which warrants further studies. Results have been disseminated at international conferences as well as online seminars and helped me to secure a position as an independent junior group leader. The InterFat data will serve as foundation for my future research endeavours.
It was technically extremely challenging and took longer than anticipated, but with the established protocol InterFat progresses beyond the state of the art. While it engages in extensive crosstalk with peripheral organs, adipose tissue itself does not seem to be highly structured. Upon isolation, however, adipose tissue can be separated into a floating fraction and a stromal vascular fraction (SVF). The floating fraction is composed of unilocular white adipocytes and tightly associated non-adipocytes, whereas mostly adipocyte precursors, immune cells, fibroblasts and endothelial cells constitute the SVF. While the SVF pellets upon isolation and is therefore easily accessible and thus at the centre of many research endeavours, InterFat shows that the floating fraction of murine visceral adipose tissue contains a significant proportion of adipocytes. It is likely that those adipocytes exhibit an entire spectrum of functional diversity, because not all adipocytes are created equal. The cells’ functions can impact the integrity adipose tissue and thus serve as rational intervention points against the obesity pandemic thereby ameliorating the socio-economic burden of metabolic disorders on the European Union and its member states.