Obesity in mice is postponed under a photic cycle oscillating at a period similar to or shorter than their endogenous circadian rhythm period length

High-fat diet (HFD)-induced obesity (DIO) is secondary to HFD-induced disruptions in the pattern and robustness of endogenous circadian rhythms and is preceded by a deceleration in the period length (tau) of these rhythms. Recently, we have shown that DIO in mice held under a 24-h light-dark cycle (T-cycle) is also secondary to disruptions due to entrainment to a near-tau T-cycle, as indicated by DIO prevention under a T-cycle oscillating at their expected tau. This work further examined this hypothesis by comparing energy homeostasis of low-fat diet (LFD) and HFD-fed mice held under a T-cycle oscillating at the tau of age-matched LFD-fed mice, to that of LFD- and HFD-fed mice under a 24-h T-cycle, T-cycle oscillating at a period faster than tau by the tau-24-h deviation (∆tau), or constant darkness (DD). Energy homeostasis of LFD-fed mice was unaffected by photic regimes. DIO onset under the 24-h T-cycle resembled that under DD, and was preceded by prevention of the HFD-induced shortening in tau. Compared to the 24-h T-cycle, DIO onset under tau-like and ∆tau T-cycles was similarly postponed, was associated with a difference in energy expenditure rather than intake, and accompanied by a T-cycle-related tau-shortening (i.e., ‘aftereffect’). These results highlight the centrality of the HFD-induced deceleration of tau in the early onset of DIO under the regular 24-h T-cycle. Correspondingly, the findings suggest that applying pharmacological agents attenuating the HFD-induced deceleration in tau and enhancing the robustness of the endogenous circadian rhythms may postpone DIO onset, even while feeding on HFD ad-libitum.