(A) Male overnight-fasted plasma insulin levels (HFD for 10 weeks). Slugfl/fl, n = 6; SlugΔLepRb, n = 6. (B) Male GTT and ITT (HFD for 13 weeks). Slugfl/fl, n = 4; SlugΔLepRb, n=5. (C) Female overnight-fasted plasma insulin levels (HFD for 10 weeks). Slugfl/fl, n = 6; SlugΔLepRb, n = 6. (D) Female GTT and ITT (HFD for 12 weeks). Slugfl/fl, n = 3; SlugΔLepRb, n = 4. (E) Slugfl/fl and SlugΔLepRb males (HFD for 13 weeks) were fasted overnight and treated with PBS (n = 3) or insulin (n = 4). Liver extracts were immunoblotted with antibodies to phospho-Akt and Akt. Phospho-Akt was normalized to Akt. (F) Liver TAG levels (normalized to liver weight; HFD for 13 weeks). Male Slugfl/fl, n = 6; male SlugΔLepRb, n = 6; female Slugfl/fl, n = 3; female SlugΔLepRb, n = 4. (G) Representative H&E staining of male liver sections (HFD for 13 weeks, n = 4 mice per group). Scale bar: 200 μm. Data are presented as mean ± SEM. *P < 0.05, 2-tailed unpaired Student’s t test (A, C, E, and F) and 2-way ANOVA (B and D).