Figure 2: Hepatocyte Tlr4 promotes HFD-induced insulin resistance in mice.

(a) Glucose tolerance test (GTT, 1.2 mg g⁻¹ BW, n=9–11) in 5-h fasted HFD-fed mice. (b) Insulin tolerance test (ITT, 1.5 mU g⁻¹ BW, n=8–10) in 5-h fasted HFD-fed mice. (c) Glucose-stimulated insulin secretion in overnight fasted mice after 8 weeks of HFD feeding. Glucose (2 mg g⁻¹ BW) were injected intraperitoneally and plasma insulin concentrations were measured at the indicated time points (n=6–7). (d–f) After 16 weeks HFD feeding, hyperinsulinemic-euglycemic (10 mU kg⁻¹ min⁻¹, 150 mg dl⁻¹, respectively) clamps of 120 min were performed in conscious, chronically catheterized, 4–5-h fasted Tlr4^fl/fl and Tlr4^LKO mice (n=6–7). (d) Glucose infiltration rate (GIR) during the 120-min clamp experiment. (e,f) Basal and insulin-stimulated (clamp steady-state (t=80–120 min)) hepatic glucose production (e, HGP) and glucose disposal rate (f). (g) Western blotting of insulin-stimulated Akt phosphorylation in epididymal fat pad from HFD-fed Tlr4^fl/fl and Tlr4^LKO mice. Representative western blot images are shown. *P<0.05, **P<0.01, ***P<0.001, compared between Tlr4^fl/fl and Tlr4^LKO mice (Student’s t-test). All data are presented as means±s.e.m.