Extended Data Fig. 7: Rosi-ATM-sEVs enhance AKT phosphorylation in all insulin target tissues and reduce pro-inflammatory ATMs.

Obese mice fed 10 weeks HFD were treated for 4 weeks with Rosi-ATM-sEVs (Rosi-ATM-sEVs), HFD-ATM-sEVs, or PBS Ctrl liposomes compared to Rosi diet: a, Insulin-stimulated AKT phosphorylation in the epididymal adipose tissue (eWAT) and liver. b, Protein expression of PPARy (descending P = 0.0170,0.0164) and its inhibitory phosphorylation sites S273 (*P = 0.0342, descending ***P = < 0.0001,0.0002,0.0001) and S112 (*P = 0.0448, **P = 0.0017, descending ***P = 0.006, < 0.0001) in the eWAT. c-e, Absolute numbers of eWAT ATMs per gram (*P = 0.0340, ***P = 0.0007) (c) and their subpopulations: Double negative (DN), CD11c⁺CD206⁻ monocyte-derived macrophages (p = 0.0010), CD11c⁺CD206^low ‘M1-like’ (**P = 0.0020, ***P<0.0001), CD11c^-CD206^high ‘M2-like’ ATMs (d), and CD9⁺ (CD9⁺, descending P = 0.0179,0.0001,0.0178, Trem2^-CD9⁺, PBS versus HFD-sEVs, P = 0.0015, HFD-sEVs versus Rosi-sEVs, P = 0.0015, ***P < 0.0001) or CD9⁺Trem2⁺ lipid-associated macrophages (LAMs, *P = 0.0387, **P = 0.0011) (e). f, Circulating leptin levels (P = 0.0301). g, Plasma particle concentration of Rosi-ATM-sEV-treated obese mice compared to Rosi mice measured by NanoSight analysis. Statistical data are expressed as mean ± s.e.m., with each data point representing a biologically independent mouse from one cohort. *P < 0.05, **P < 0.01, ***P < 0.001, with one-way ANOVA, followed by Tukey′s multiple comparisons tests (c-f) or an unpaired Mann-Whitney U-test with two-tailed distribution (g).

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