1685-P: Comparison of Obesity and Aging Signatures in Murine Adipose Tissue at Single-Cell Resolution

Abstract

Obesity and aging are major risk factors for various diseases and thus represent heavy socioeconomic burden to global healthcare. The two processes share similar, if not convergent, phenotypes, and increasing evidence suggests that one accelerates the other. Both obesity and aging are associated with insulin resistance, chronic low-grade inflammation and dysfunction of systemic energy homeostasis. However, there are many differences as well and the molecular mechanisms behind such similarities and differences remain unclear. Dysfunction of adipose tissue plays a significant role in both processes. Many studies have characterized adipose tissue of lean and obese mice at single-cell level, but obese and aged adipose tissue have not been directly compared side-by-side. Here, we compare single-cell transcriptomics of visceral (VAT) and subcutaneous (SAT) white adipose tissue in lean, diet-induced obesity, and aged conditions. In obese VAT, the relative frequency of macrophages increased, while that of lymphocytes decreased as expected. However, such myeloid shift was not observed in aged VAT. Metabolically, TREM2+ “lipid-associated macrophages”, which is known to increase in obese VAT, did not increase in aged VAT. Clustering of mesenchymal progenitor cells revealed depot-specific differences in previously reported cell subtypes. More cells were in a further differentiated, committed stage in VAT than in SAT. CD142+ CLEC11A+ “Aregs,” which were previously found to inhibit adipogenesis, increased in aged VAT and obese SAT. Interestingly, the frequency of endothelial cells in obese or aged state drastically decreased in SAT but not in VAT. Our comparative single-cell transcriptome atlas provides a detailed resource to analyze functional genomics behind obesity and aging. Disclosure E.Lee: None. D.Kang: None. J.Suh: None.