Fig. 4

PPIs enhance the therapeutic effects of RBC-EVs/Trim21-ASOs on obesity-related metabolic disorders. (A) Mice were intravenously injected with 50 µg PKH26-labeled RBC-EVs/Trim21-ASOs and simultaneously received intraperitoneal injection with 5 mg kg−1 Rabe. RBC-EVs/Trim21-ASOs in isolated F4/80+ liver macrophages were analyzed by flow cytometry. (B–F) Male mice were fed an HFD for 16 weeks and then injected with RBC-EVs/Trim21-ASOs alone or combined with Rabe from a specific time point. Body weights (B), GTT (C), ITT (D), plasma ALT and AST levels (E), representative ORO staining of liver sections (F). Scale bar, 50 μm. ns, not significant; *P < 0.05; **P < 0.01; ***P < 0.001 (one-way ANOVA followed by Tukey test except for unpaired two-tailed Student’s t-test in A; mean ± SD).