Fig. 7: Irisin improves metabolic health largely through ST2+ Treg cells.
From: Irisin ameliorates obesity and insulin resistance via adipose tissue IL-33 and regulatory T cells
a, Schematic of HFD feeding experiment with male ST2 Treg null mice (Il1rl1Δtreg) and their littermates (Il1rl1wt). Mice received AAV-irisin or AAV-GFP at 4 weeks old and were then fed a HFD for 17 weeks. GTTs and ITTs were performed with mice fed a HFD for 12 weeks. Flow cytometric analysis was performed with mice fed a HFD for 17 weeks. b–d, Flow cytometric analysis of the number of total Treg cells and the fraction of ST2+ Treg cells (n = 11, 10, 4, 7) (b), the number of total CD45+ cells, the percentages of total and CD11chi macrophages (c, top), the percentages of total T cells, CD8+ T cells and Foxp3−CD4+ cells (c, bottom) and the number of total mSCs and the fraction of IL-33+mSCs (d) One-way ANOVA was used for calculating P values (b: ****P < 0.0001, ****P < 0.0001 and ****P < 0.0001; c, top: ***P = 0.00011, ***P = 0.00074, *P = 0.038; ****P < 0.0001, *P = 0.031 and ****P < 0.0001; c, bottom: ****P < 0.0001, *P = 0.036, ****P < 0.0001, ****P < 0.0001 and **P = 0.0015; d: ****P < 0.0001, *P < 0.027 and *P < 0.018). e, GTT and ITT analyses of the indicated mice fed a HFD for 12 weeks (n = 11, 10, 4, 7). Two-way ANOVA was used for calculating P values (GTT: ****P < 0.0001, and **P = 0.0093; ITT: ****P < 0.0001, and **P = 0.0015). Note, normalized values are presented for this plot because multiple independent cohorts were examined at diverse times. f, RT–qPCR measuring mRNAs associated with thermogenesis and adipogenesis in iWAT of the indicated male mice received AAV-irisin or AAV-GFP, and fed a HFD for 17 weeks (n = 11, 10, 4, 7). Two-way ANOVA was used for calculating P values (P values between Il1rl1wt AAV-GFP and Il1rl1wt AAV-irisin, as well as Il1rl1wt AAV-irisin and Il1rl1Δtreg AAV-irisin: Ppargc1a: ***P = 0.0004 and ***P = 0.0006; Ucp1: ****P < 0.0001 and **P = 0.0043; Ckb: ***P = 0.0002 and NS P = 0.6285; Alpl: **P = 0.0050 and NS P = 0.9976; Dio2: **P = 0.0048 and *P = 0.0123; Elovl3: ****P < 0.0001 and ****P < 0.0001). Mean ± s.d.*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Significant but irrelevant P values are not indicated. Unless specifically mentioned, experiments were repeated twice with similar results. Mouse illustration in a created in BioRender; A, M. https://biorender.com/5v6fzeu (2026).
