Clock system disruption in male Fischer 344 rats fed cafeteria diet and administered sweet treats at different times: The zeitgeber role of grape seed flavanols

Abstract

Current lifestyles include calorie-dense diets and late-night food intake, which can lead to circadian misalignment. Our group recently demonstrated that sweet treats before bedtime alter the clock system in healthy rats, increasing metabolic risk factors. Therefore, we aimed to assess the impact of the sweet treat consumption time on the clock system in rats fed a cafeteria diet (CAF). Moreover, since flavanols have demonstrated beneficial effects in metabolic disorders and clock gene modulation, we also investigated whether these phenolic compounds can restore the circadian disruption caused by these altered dietary patterns. For this, 64 Fisher rats were fed CAF for 9 weeks. In the last 4 weeks, animals were daily administered a low dose of sugar (160 mg/kg) as a sweet treat at 8 a.m. (ZT0) or 8 p.m. (ZT12). Two other groups received 25 mg/kg of grape seed flavanols in addition to sweet treats. Finally, the animals were sacrificed at different time points (9 a.m., 3 p.m., 9 p.m., and 3 a.m.). The results showed that metabolic and circadian disturbances by CAF may be influenced by the time of sugar administration, slightly reinforcing the alterations in diurnal rhythmicity of serum biochemical parameters, hormones, and hypothalamic genes with bedtime snacking. Flavanols improved metabolic health and restored the oscillation of biochemical parameters, hormones, and clock and appetite-signaling genes, showing greater effects at ZT12. These results highlight the importance of meal timing in influencing physiological and metabolic outcomes, even under calorie-dense diets. Moreover, they also suggest the zeitgeber role of flavanols, modulating the clock system and contributing to an improved metabolic profile under different feeding pattern conditions.

Keywords: Chrononutrition; circadian rhythms; cosinor; metabolism; snack timing; zeitgebers.