Figure 1. Hepatic autophagy activation is essential for exercise-induced insulin sensitization against high-fat diet (HFD).

(A) Hepatic ATG7 knockdown efficiency and experimental design using ATG7^Δliver mice. WT mice were intravenously (i.v.) injected with control AAV (control mice) or AAV2/8-miR30-TBG promoter-mCherry-shATG7 (ATG7^Δliver mice). The remaining ATG7 expression in ATG7^Δliver mice is likely derived from other non-hepatocyte cell types in the liver. (B) Comparable body weight of control and ATG7^Δliver mice under HFD feeding, with or without daily exercise for 7 weeks. N=5–12. (C) Glucose tolerance test (GTT) and insulin tolerance test (ITT) of control and ATG7^Δliver mice fed with HFD with or without daily 50-min treadmill exercise for 7 weeks. AUC, area under the curve. N=5–12. (D) Western blot (WB) analysis of insulin-stimulated Akt phosphorylation/activation in the liver of control and ATG7^Δliver mice fed with HFD with or without daily 50-min exercise for 7 weeks, and then injected with 2 U/kg insulin 15 min prior to tissue collection. The “- insulin resting” controls were loaded twice on both gels to allow for normalization of samples to the same controls. N=3. One-way ANOVA with Tukey-Kramer test. *, #, ¶, P<0.05; **, ##, ¶¶, P<0.01; ***, ¶¶¶, P<0.001; NS, not significant.