SUN-635 Sex Differences in Human Adipose Cellular Populations via Single Nuclei RNA Sequencing

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Abstract Disclosure: A. Aslamy: None. J. Nie: None. M.K. Semwal: None. S. Espinoza: None. N. Musi: None. Increased adiposity is the leading cause of metabolic disease. Sex differences have been shown in adipose tissue distribution, morphology, and function, however, changes in distinct cell populations have not been investigated in humans. With the advent of single nuclei (sn)-RNA sequencing (seq), we can identify differences in adipose cell (sub)populations that were previously challenging to determine due to the heterogenous nature of bulk adipose tissue. To examine differences in cellular populations based on sex, we obtained subcutaneous adipose tissue from non-diabetic, older individuals: N=16 women (average age 73.4 ±1.0 years; average BMI 26.6 ±4.1 kg/m2) and N=17 men (average age 70.6 ± 3.8 years; average BMI 27.5 ± 5.5 kg/m2). Using sn-RNA seq, we identified a novel adipocyte subpopulation, termed “PG1” that is more abundant in women vs. men (p = 0.048). Gene ontology analysis of molecular function for the PG1 subpopulation reveals that this subpopulation has significant phosphatase and ligase activity. Additionally, we discovered increased numbers of fibroinflammatory progenitors (p = 0.018) and mast cells (p = 0.013) in women vs. men, whereas higher levels of lipid-associated macrophages (p= 0.013) were found in men. There were no significant differences in any other adipocyte, stromovascular, or immune cell populations based on sex. Overall, our data suggests that differences in PG1, fibroinflammatory progenitors, and/or immune cells may contribute to functional differences in adipose tissue between men and women. Further investigation into the mechanisms behind these sex differences could be key to developing novel, precision-based therapies for obesity and metabolic disease. Presentation: Sunday, July 13, 2025

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