Fig. 2: Distinct fuel utilization patterns of 3xTg-AD mice under reduced caloric intake conditions.

Metabolic chambers were used to determine fuel source utilization and energy expenditure 24 hours in female (A–D) and male (E–H). Six-month-old female and male 3xTg-AD mice were placed on either ad libitum (AL), Diluted AL (DL) or Caloric Restricted (CR with fasting between once-daily meals) diet and phenotyped over the course of the next 9 months. A Respiratory exchange ratio (RER) over 24hrs in females. (B) RER in light, dark and combined cycles in females. C Energy expenditure (EE) over 24 hrs in females. (D) EE normalized to body weight in females during light, dark and combined cycles in females. (E) RER over 24 hrs in males. (F) RER in light, dark and combined cycles in males (AL vs CR *p < 0.0001, DL vs CR *p < 0.0001 (light), AL vs CR *p = 0.0016, DL vs CR *p = 0.0006 (dark)). (G) EE over 24 hrs in males. (H) EE normalized to body weight in males during light, dark and combined cycles in males. A–D n = 6 AL, n = 6 DL and n = 5 CR-fed biologically independent 3xTg female mice were used. E–H n = 5 AL, n = 5 DL and n = 6 CR fed biologically independent 3xTg male mice were used. B, D, F, H (Left panel) Statistics for the overall effect of diet (D), time (T), and the interaction (DxT) represents the p values from a two-way ANOVA; *p < 0.05 from a two-tailed Sidak’s post-test examining the effect of parameters identified as significant in the two-way ANOVA. The overall effect of sex (S) represents the p value from a separately completed three-way ANOVA. (Right panel) *p < 0.05, two-tailed Tukey’s test post one-way ANOVA. Data represented as mean ± SEM. Source data are provided as a Source Data file.