Researchers at Karolinska Institutet and AstraZeneca have discovered that gene expression in adipose stem cells varies according to sex and type of adipose tissue in mice. The study shows that female adipose stem cells express higher levels of estrogen and progesterone receptors, while male cells express a gene that encodes for an enzyme that deactivate estrogens. These findings may pave the way for future therapeutic interventions to increase the body's fat storage capacity and improve metaboli
What does your publication show?
"We have found that the gene expression of adipose 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 stem cells that can guide future studies in the field," says Martin Uhrbom, Phd Student, at the Department of Medicine, Huddinge.
"For example, female adipose stem cells express higher levels of the estrogen (Esr1) and progesterone (Pgr) receptors, whereas male cells express Sulfotransferase family 1E member 1 (Sult1e1), an enzyme that deactivates estrogens. Moreover, two genes associated with higher blood pressure, angiotensin (Agt) and Angiotensin converting enzyme (Ace), are enriched in male adipose stem cells."
Why are the results important?
"Adipose stem cells play a crucial role in the expansion of adipose tissue since these cells can differentiate into new mature adipocytes, that are the fat-storing units of our body. Over-feeding can lead to obesity and impaired metabolism of adipose tissue which consequently can provoke unwanted redistribution of lipids to non-adipose tissue such as skeletal muscle and heart, causing insulin resistance and increased blood glucose levels. It is therefore highly desirable to gain more knowledge on how the fat storage capacity of adipose tissue can be increased. In this aspect adipose stem cells may play an important role, with future therapeutic interventions aimed to increase their ability to differentiate to mature adipocytes and by so increase our fat storing capacity."
How did you preform the study?
"We have used single cell RNA sequencing and 3D rendering imaging to better characterise adipose stem cells in mice. In addition, we have validated our findings using publicly available datasets."
What is the next step in your research?
"The next step is to focus on specific signalling pathways that can influence the ability of adipose stem cells to differentiate into mature adipocytes as well as investigating the relevance to human biology."
AstraZeneca was the main funder of the study.
Publication
"Adipose stem cells are sexually dimorphic cells with dual roles as preadipocytes and resident fibroblasts" Uhrbom M, Muhl L, Genové G, Liu J, Palmgren H, Alexandersson I, Karlsson F, Zhou AX, Lunnerdal S, Gustafsson S, Buyandelger B, Petkevicius K, Ahlstedt I, Karlsson D, Aasehaug L, He L, Jeansson M, Betsholtz C, Peng XR. Nat Commun 15, 7643, Online 2 September, 2024, DOI: 10.1038/s41467-024-51867-9.
