Depot-specific differences and heterogeneity of adipose-derived stem cells in diet-induced obesity.

Abstract

Objective: Obesity is a global health concern. Studying the heterogeneity of adipose-derived stem cells (ADSCs) plays a pivotal role in understanding metabolic disorders, such as obesity.

Methods: Mass cytometry was used to determine the depot-specific differences and heterogeneity of ADSCs and their alterations at the single-cell level in a diet-induced-obesity (DIO) model in which mice were treated with liraglutide.

Results: We characterized the relationship among ADSC markers and found that CD26 and CD142 could identify the most representative heterogeneous ADSCs in subcutaneous adipose tissue and visceral adipose tissue. Specifically, CD26⁺CD142^- and CD26⁺CD142⁺ ADSCs were exclusive to subcutaneous adipose tissue and visceral adipose tissue, respectively, whereas CD26^-CD142⁺ ADSCs were present in both. RNA analysis explored the potential functions of these three subgroups. In the visceral adipose tissue of DIO mice, we observed a substantial downregulation of CD26⁺CD142⁺ ADSCs and upregulation of CD26^-CD142⁺ ADSCs, both of which were mitigated by liraglutide treatment.

Conclusions: Our study highlights the depot-specific differences and heterogeneity of ADSCs and their alterations under DIO conditions, which can potentially be reversed by liraglutide treatment. This study provides new insights into the identification of more specific ADSC subgroups to explore the etiology of metabolism-related diseases.