Extended Data Fig. 9: Irisin’s effects in obese mice in a therapeutic setting.
From: Irisin ameliorates obesity and insulin resistance via adipose tissue IL-33 and regulatory T cells

6-week-old male C57BL6/J mice were switched to HFD feeding. After 14 weeks, mice were intravenously injected with AAV-GFP (n = 15) or AAV-Irisin (n = 15). After another 10 weeks of HFD feeding, mice were subjected to metabolic analysis and finally sacrificed for tissue analysis. (A) Schematic of the HFD experiment. (B) ELISA measurements of irisin plasma concentrations in mice; n = 15, 15. Unpaired two-sided T-test was used for calculating p values (*** p = 0.0004). (C) Body weight measurements (n = 15, 15). (D) Body composition analysis by MRI (n = 15, 15). Unpaired two-sided T-test was used for calculating p values. (E) Intraperitoneal glucose tolerance tests (GTTs) (n = 15, 15). Two-way ANOVA was used for calculating p values. (F) Intraperitoneal insulin tolerance tests (ITTs) (n = 15, 15). Two-way ANOVA was used for calculating p values. (G–I) Energy expenditure measured (G), accumulated food intake (H) and distance traveled (I) in CLAMS cages over one week. n = 8, 8. The last 4.5 days of measurement were shown on the left and the averaged values in the light and dark periods were summarized on the right. Unpaired two-sided T-test was used for calculating p values. (J) RT-qPCR measuring mRNAs associated with thermogenesis and adipogenesis in iWAT (left) (n = 8, 8) and eWAT (right) (n = 7, 7) of HFD-induced obese mice received AAV-irisin or -GFP for 10 weeks. Two-way ANOVA was used for calculating p values (* p = 0.0170, ** p = 0.0061, and ** p = 0.0036). (K–O) Flow-cytometric analysis of the number of total CD45+ cells (K), percentages of total (L) and CD11chigh (M) macrophages, and total T, CD8+ and Foxp3− CD4+ T cells (N), as well as Treg cells and ST2+ Treg cells in eWATs from obese mice administered AAV for 10 weeks (n = 8, 8). Unpaired two-sided T-test was used for calculating p values (* p = 0.0173). Abbreviations as per Figs. 1 and 2. Mean ± SD.* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001, ns: not significant. 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).