Obesity reshapes regulatory T cells in the visceral adipose tissue by disrupting cellular cholesterol homeostasis.

ABSTRACT: Regulatory T cells (T_regs) accumulate in the visceral adipose tissue (VAT) to maintain systemic metabolic homeostasis but decline during obesity. Here, we explored the metabolic pathways controlling the homeostasis, composition, and function of VAT T_regs under normal and high-fat diet feeding conditions. We found that cholesterol metabolism was specifically up-regulated in ST2^hi VAT T_reg subsets. T_reg-specific deletion of Srebf2, the master regulator of cholesterol homeostasis, selectively reduced ST2^hi VAT T_regs, increasing VAT inflammation and insulin resistance. Single-cell RNA/T cell receptor (TCR) sequencing revealed a specific loss and reduced clonal expansion of ST2^hi VAT T_reg s

SUBMITTER: Elkins C 

PROVIDER: S-EPMC11786953 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature