Fig. 1.

Study setup, rhythms of behaviour, and energy balance. APOE∗3-Leiden.CETP mice were exposed to 6-h phase advancement every 3 days (circadian disturbance; CD) or regular 12:12 light–dark cycle (Control), while having either ad libitum food access (AL) or food access during the dark phase only (time-restricted feeding; TRF). (A) The shifts in light–dark cycle are displayed for the first 11 days, covering four shifts. Mice were subjected to the intervention for a total duration of 14 weeks. Prior to the first shift, mice were subjected to a dietary run-in period for 22 days on a normal light–dark cycle. A timeline is provided displaying in vivo measurements with corresponding duration or time point(s) (in Zeitgeber Time (ZT)). (B) Actograms of four consecutive shifts during days 12–23 of the study were constructed (and double-plotted) and periodogram analysis was used to calculate (C) rhythm strength (expressed as A.U., arbitrary unit) and (D) period (n = 3–6 cages of 2–3 mice/group). During days 61–63, mice were housed in metabolic home-cages for continuous measurement of (E, F) food intake and (G, H) energy expenditure (EE), after which the percentage of each parameter during the light phase and the total levels were calculated (n = 4–7 cages of 2–3 mice/group). Data are presented as means ± SD. ∗ Control + AL vs. CD + AL; ^&Control + TRF vs. CD + TRF. ∗p < 0.05; ∗∗∗^,&&& p < 0.001, according to unpaired t-test (D) or two-way ANOVA and following Tukey's multiple-comparison test (B–C, E–G). (A) was created with BioRender.com.