Figure 11.
AAV8L-delivered Osr1 expression rescued NAFLD/NASH of the Osr1ΔMφmice. (A) Schematic diagram for the study design with special diet treatment and AAV infection. Mice were injected with pAAV8L-control or pAAV8L-Osr1 at the dosage of 1.0 × 1010 gc/mouse at wean (3 weeks of age) through retro-orbital venous sinus delivery, followed by HFD or MCD treatment for either 14 or 4 weeks. The time point when the fluorescence-activated cell sorting (B), Western blot (C), and IF staining (D) were conducted were indicated. (E) Body weight at sacrifice. Mice were fed with HFD for 14 weeks. (F) Intraperitoneal glucose tolerance test (IPGTT) results at 12 weeks of HFD and associated quantification. (G) Liver weight upon HFD treatment. (H) Representative hematoxylin and eosin (H&E) staining and NAS scoring under HFD and MCD treatment. (I) Representative IF staining of F4/80 and quantification. (J) Macrophage polarization in the liver. (K) Pro-inflammatory cytokines mRNA level. M1 and M2 macrophages were identified as CD45+F4/80+CD11b+MHCII+ CD206- and CD45+F4/80+CD11b+CD206+ MHCII-, respectively. Results are presented as means ± standard error of n = 5 independent experiments. Significant differences are indicated as follows: ∗P < .05; ∗∗P < .01.