Transcriptional Changes in Isolated Human Adipocytes During Obesity

Overview

Adipocytes play an important role in our body through their function as metabolic energy stores in the form of fat deposits, which are stored when metabolic energy is in excess and released when energy levels are low. In severe obesity, adipose tissue grows through the production of more adipocytes from stem cells (hyperplasia) and the increase in the size of existing adipocytes (hypertrophy). This ability of adipocytes, to maintain their functionality during tissue expansion, is critical in determining the development of obesity-related comorbidities. However, not all adipocytes are the same as adipocyte function differs greatly depending on the depot in which they are found. To elucidate the mechanisms underlying adipocyte adaptability, it is necessary to obtain a deep systems biology understanding of how signaling in different types of adipocytes regulates metabolism and function. Currently, this research group is conducting a systems biology analysis of adipocyte plasticity in obesity in mouse models, but adipose tissue biopsies from different depots in humans are lacking and needed to investigate the regulation of adipocyte function and plasticity in humans. Such studies of adipocytes are crucial for the understanding how obesity affects adipose tissue function and leads to comorbidities.

The development of overweight and obesity is associated with major changes in adipose tissue, including structural changes in cell type composition as well as gene expression in individual adipose tissue cell types. The molecular mechanisms underlying these changes are not yet known. The investigators therefore hypothesized that overweight and obesity cause changes in the transcriptional program of adipocytes and this leads to impaired function of adipocytes. This study will use advanced genomic technologies available that can measure the dynamic changes in the transcriptome and genomic landscape of isolated adipocytes from patient biopsies, to better understand which changes in the adipocytes in particular underlie the severe comorbidities that occur with the development of obesity. It is expected that the described project will contribute important knowledge about adipocyte-specific transcriptional programs that play a crucial role in obesity. This and thus may contribute to the knowledge required to develop adapted- and personalized medicines, or new therapeutic approaches to treat obesity and its associated diseases. Recruitment of 100 subjects will be from patients referred for surgical cholecystectomies, herniotomies or similar operations at Bispebjerg Hospital. The control group will consist of study participants with a BMI ≥ 19 kg/m2 and \< 25 kg/m2, and the "case" group will consist of study participants with a BMI ≥ 25 kg/m2. When including subjects, emphasis will be placed on achieving a control group of approximately 25 subjects and a "case" group of approximately 75 subjects with varying degrees of elevated BMI.