1. Treatment with AAV8‐hAAT‐FGF21 improves insulin sensitivity and glucose tolerance
Treatment with AAV8‐hAAT‐FGF21 improves insulin sensitivity and glucose tolerance AFasted and fed blood glucose levels in mice fed a chow or HFD and injected with either AAV8‐hAAT‐null or different doses of AAV8‐hAAT‐FGF21 vectors as young adults or as adults.BFasted and fed serum insulin levels in the same groups of animals as in (A).Cβ‐Cell mass in the group of animals that initiated the HFD feeding and received FGF21 vectors as adults.D, EInsulin sensitivity was determined in all experimental groups after an intraperitoneal injection of insulin (0.75 units/kg body weight). Results were calculated as the percentage of initial blood glucose levels. During the ITT, basal (t = 0 min), peak (t = 60 min), and final (t = 90 min) glycemia were 166.4 ± 5.7, 37.9 ± 5.2, and 62.4 ± 8.2 mg/dl, respectively, in HFD‐fed mice treated as young adults with 5 × 1010 vg of AAV8‐hAAT‐FGF21 vectors.FGlucose tolerance was studied in the group of mice that initiated the HFD feeding and received FGF21 vectors as young adults after an intraperitoneal injection of glucose (2 g/kg body weight).GSerum insulin levels during the glucose tolerance test shown in (F).Data information: All data represent the mean ± SEM. In (A, B, D, E), young adults: AAV8‐hAAT‐null chow (n = 10 animals), AAV8‐hAAT‐null HFD (n = 8), AAV8‐hAAT‐FGF21 HFD 1 × 1010 vg (n = 9), and 5 × 1010 vg (n = 8). Adults: AAV8‐hAAT‐null chow (n = 7), AAV8‐hAAT‐null HFD (n = 7), AAV8‐hAAT‐FGF21 HFD 1 × 1010 vg (n = 7), 2 × 1010 vg (n = 8), and 5 × 1010 vg (n = 7). In (C), adults: AAV8‐hAAT‐null chow (n = 5), AAV8‐hAAT‐null HFD (n = 5), AAV8‐hAAT‐FGF21 HFD 1 × 1010 vg (n = 4), 2 × 1010 vg (n = 5) and 5 × 1010 vg (n = 5). In (F, G), n = 6 animals/group. In (A–G), data were analyzed by one‐way ANOVA with Tukey's post hoc correction. *P < 0.05, **P < 0.01, and ***P < 0.001 versus the chow‐fed null‐injected group. #P < 0.05, ##P < 0.01, and ###P < 0.001 versus the HFD‐fed null‐injected group. HFD, high‐fat diet.
Veronica Jimenez et al. EMBO Mol Med. 2018;emmm
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