Fig. 1

Long-term HFD feeding induces peripheral and brain insulin resistance in A7-Tg mice. a Monthly body weight changes of male A7-Tg mice (Chow: n = 12; HFD: n = 11). b,c Fasting plasma insulin (b) and blood glucose levels (c) of 9-month-old male A7-Tg mice (Chow: n = 12; HFD: n = 11). d Blood glucose levels during an insulin tolerance test (ITT, 0.75 U/kg body weight, left) and the area under the curve (AUC) of blood glucose (right) of 9-month-old male A7-Tg mice (Chow: n = 12; HFD: n = 10). e, f Levels of phosphorylated IR in the brain upon insulin administration. A7-Tg mice were intraperitoneally injected with PBS or insulin and cortical lysates were immunoprecipitaed with an anti-IR antibody followed by immunoblotting with anti-phospho Tyr and anti-IR antibodies at 5 (e, Chow-PBS: n = 3; Chow-insulin: n = 6; HFD-PBS: n = 4; HFD-insulin: n = 6) and 9 (f, Chow-PBS: n = 6; Chow-insulin: n = 6; HFD-PBS: n = 5; HFD-insulin: n = 6) month of age (upper panels). Relative levels of signal intensity are shown (lower panels). g Blood glucose levels during hyperinsulinemic glucose clamps (Chow: n = 7; HFD: n = 6). h Plasma insulin levels during the clamps (Chow: n = 7; HFD: n = 6). i Correlation plots between the ISF insulin and the average plasma insulin levels during the clamps in chow and HFD-fed A7-Tg mice (Chow: n = 7; HFD: n = 6). j ISF to plasma insulin ratio (Chow: n = 7; HFD: n = 6). Data are mean ± SEM. *p < 0.05, **p < 0.01, *** p < 0.001 (repeated-measures ANOVA with Sidak’s post-hoc test, a, d; unpaired t test, b, c, d, j; two-way ANOVA with Tukey’s post-hoc test, e, f; Spearman’s correlation, i)