Fig. 7: TIPE2 restoration in VAT macrophages reduces ASC ferroptosis and metabolic disorders in HFD-fed M-Tipe2-/- mice.

a–e Body weight change (a), glucose tolerance test (b) and insulin tolerance test (c) with corresponding area under the curve (d, e) in M-Tipe2+/+ and M-Tipe2-/- mice received M-TIPE2 (recombinant AAV expressing EGFP-fused TIPE2 in F4/80+ macrophages) in visceral fat 2 weeks after HFD intervention (12 weeks). f, g Ratios of EpiVAT mass (f), liver weight (g) to body weight. h Statistical analysis of adipocyte sizes in VAT sections (n ≥ 262 adipocytes examined over 3 mice per group). i Representative confocal imaging of immunofluorescence for 4-HNE (red) in ASCs (Sca-1, green) in VAT sections. Scale bars, 10 μm. j–m Flow cytometry frequencies of ASCs in SVF (j, k), mitochondrial ROS in ASCs (j, l), cellular death in ASCs (j, m) in VAT of the mice. n = 3 or 4 mice per group (a–g; k–m). Data are presented as mean ± s.e.m. #P < 0.05, ##P < 0.01, ###P < 0.001 (M-Tipe2+/++MOCK vs. M-Tipe2-/-+MOCK in a–c); *P < 0.05, **P < 0.01, ***P < 0.001 (M-Tipe2-/-+MOCK vs. M-Tipe2-/-+M-TIPE2 in a–c) determined by two-way (a–c) or one-way ANOVA (d–h,k–m).