Adipose tissue plasticity in obesity

Obesity has spread worldwide to pandemic levels and it is now recognized that obesity is one of the major contributorsto health complications globally. Obesity is associated with an increased amount of adipose tissue that can lead to co-morbidities, such as type 2 diabetes, cardiovascular diseases, cancers, and liver failures. The rising prevalence of obesity among children and young people gives rise to an increased burden of obesity-associated diseases in the future to come. Thus, understanding the etiology of co-morbid conditions that arise with obesity progression is important for restoring metabolic health. Advances in single-cell technologies have revolutionized how we can
study disease mechanisms. The cellular resolved insights into health and disease may drive new concepts of disease management.


The overarching aim of this PhD study was to obtain a cellular resolved insight into the changes that adipose tissues undergo while adapting to obesity. We applied single-nucleus RNA-sequencing to isolated nuclei from murine adipose tissue to study the cellular plasticity in obesity. Using the nuclear transcriptomes, we were able to reconstruct the process of adipocyte differentiation in vivo – a process that has been linked to improved metabolism in obesity. In Part I, this work will be discussed in the context of adipogenesis. Additional adipogenic trajectories are further presented, indicating that all of our previously identified progenitor populations may have capacity for
adipogenesis.


Recent adaptations to our nuclei isolation protocol allow for the isolation of nuclei from adipose tissue samples of limited size. In Part II, our optimized protocol was applied on human adipose tissue followed by single-nucleus RNA-sequencing to demonstrate that our protocol generates transcriptomic data from individual nuclei of high quality.