Fig. 3: Fasting is required for CR-induced insulin sensitivity in both female and male 3xTg-AD mice.

Glucose (A) and insulin (B) tolerance tests were performed in female mice after three months on ad libitum (AL), Diluted AL (DL) or Caloric Restricted (CR with fasting between once-daily meals) fed diets. A GTT: n = 6 3xTg biologically independent mice per group. B ITT: n = 6 3xTg biologically independent mice per group. Glucose (C) and insulin (D) tolerance tests were performed in male mice after three months on AL, DL or CR fed diets. C GTT: n = 6 AL, n = 5 DL and n = 6 CR fed 3xTg biologically independent mice. (D) ITT: n = 6 AL, n = 5 DL and n = 6 CR fed biologically independent mice. E Heat map representation of all the metabolic parameters in 3xTg and NTg female and male mice. Color represents the log2 fold-change vs. AL fed mice. A–D Statistics for the overall effects of diet (D), sex (S) and their interaction (DxS) represent the p values from a 2-way ANOVA; *p < 0.05, from a two-tailed Tukey’s test post ANOVA. A AL vs DL *p = 0.0065. (B) DL vs CR *p = 0.0018. (C) AL vs CR *p = 0.0030. (D) AL vs CR, DL vs CR *p < 0.0001. Data represented as mean ± SEM. NTg, Non-transgenic control, AUC, Area Under the Curve. Source data are provided as a Source Data file.