Fig 1: No bone abnormalities were observed in AAV8-hAAT-FGF21-treated animalsThe long-term effects of FGF21 gene transfer on bones were studied by comparison of HFD-fed mice treated with the highest dose (5 × 1010 vg/mouse) of FGF21 vectors as young adults or adults with null-injected, chow or HFD-fed animals. ATotal naso-anal length.BTibial length.C–OMicro-computed tomography (µCT) analysis of the epiphysis (C–J) and the diaphysis (K–O) of tibiae obtained at the time of sacrifice, that is, when animals were 18 months of age, from HFD-fed mice administered with either null or FGF21-encoding AAV vectors.P, QCirculating IGFBP1 (P) and IGF1 (Q) levels measured by ELISA.Data information: All data represent the mean ± SEM. In (A, P, Q), 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 (B–O), n = 4 animals/group. In (A, B, P, Q), data were analyzed by one-way ANOVA with Tukey's post hoc correction. In (C–O), data were analyzed by unpaired Student's t-test. **P < 0.01 and ***P < 0.001 versus the chow-fed null-injected group. HFD, high-fat diet; BMD, bone mineral density; BMC, bone mineral content; BV, bone volume; BV/TV, bone volume/tissue volume ratio; BS/BV, bone surface/bone volume ratio; Tb.N, trabecular number; Tb.Th, trabecular thickness; Tb.Sp, trabecular separation.