Fig. 1: HFD consumption combined with STZ injection aggravates learning and memory impairments in mice.

a A schematic illustration of the chronological order of HFD feeding, STZ injection, intraperitoneal glucose tolerance test (IPGTT) testing, intraperitoneal insulin tolerance test (IPITT) testing and cognitive testing. b, The MWM test traces for NCD and HFD/STZ mice (n = 8 per group). c The HFD/STZ mice showed delayed MWM escape latency compared with NCD mice (****P < 0.0001 days 3–5, ***P = 0.006 day 6). d, e The number of platform crossings (d) and target quadrant retention time (%) (e) during the probe trial of the MWM test were lower in the HFD/STZ group than in the NCD group (**P = 0.0032 in d, **P = 0.0012 in e between the NCD and HFD/STZ groups). f The lower alternated triplets (%) in the Y-maze for HFD/STZ mice (**P = 0.0084; n = 8 per group). g, h The brain sections from the NCD-fed or HFD/STZ-induced mice were stained with the filipin probe (g); the immunofluorescence intensity of filipin⁺ cholesterol was quantified and shown (h) (n = 6 per group). i–l Linear regressions of MWM escape latency against: i serum TG, j T-CHO (total cholesterol), k LDL-C, and l hippocampal free cholesterol (Filipin fluorescence). m–p Linear regressions of Y-maze alternation (%) against the same indices: m TG, n T-CHO, o LDL-C, and p hippocampal free cholesterol. NCD (red circles) and HFD/STZ (yellow squares) are shown separately. The data are means ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. The two-tailed unpaired Student’s t-test was used in d–f and h and one-way ANOVA with Tukey’s post hoc test in c, and correlations were assessed via linear regression in i–p. See also Supplementary Fig. 1 for more information.