Study shows gender-specific gene expression in adipose tissue stem cells of mice

Researchers at Karolinska Institutet and AstraZeneca have discovered that gene expression in fat stem cells in mice varies depending on sex and type of fat tissue.

The study, published in Nature communicationshows that female adipose stem cells express higher levels of estrogen and progesterone receptors, while male cells express a gene encoding an enzyme that deactivates estrogens.

According to Martin Uhrbom, a PhD student at the Faculty of Medicine in Huddinge, the team used “single-cell RNA sequencing and 3D rendering imaging to better characterize fat stem cells in mice. In addition, we validated our results using publicly available data sets.”

These findings could pave the way for future therapeutic interventions to increase the body's fat storage capacity and improve metabolism.

“We found that gene expression of adipose tissue stem cells in male and female mice varies depending on sex and type of adipose tissue. We present a sexually dimorphic gene signature of adipose tissue stem cells that can serve as a guide for future studies in this field,” says Uhrbom.

“For example, female adipose stem cells express higher levels of estrogen (Esr1) and progesterone (Pgr) receptors, while male cells express sulfotransferase family 1E member 1 (Sult1e1), an enzyme that deactivates estrogens. In addition, two genes associated with elevated blood pressure, angiotensin (Agt) and angiotensin-converting enzyme (Ace), are enriched in male adipose stem cells.”

Commenting on the relevance of the study, Uhrbom says: “Adipose stem cells play a crucial role in the proliferation of adipose tissue, as these cells can differentiate into new mature adipocytes, which are the fat-storing units of our body.”

“Excessive nutrition can lead to obesity and impaired adipose tissue metabolism, which in turn can cause undesirable redistribution of lipids to non-adipose tissues such as skeletal muscle and heart, causing insulin resistance and elevated blood glucose levels.

“It is therefore highly desirable to learn more about how to increase the fat storage capacity of adipose tissue. In this regard, adipose stem cells could play an important role. Future therapeutic interventions could aim to increase their ability to differentiate into mature adipocytes and thus increase our fat storage capacity.

“The next step is to focus on specific signaling pathways that may influence the ability of adipose stem cells to differentiate into mature adipocytes and investigate their relevance to human biology.”