Circadian regulation of chronic rest phase snacking

• Applicant: Dr. Kimberly Begemann
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 567952185

Endogenous timekeepers termed circadian clocks enable organisms to synchronize their physiology to external daily rhythms such as the light-dark cycle. Thereby, a master circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus synchronizes subordinated CNS oscillators and peripheral tissue clocks. Circadian misalignment, i.e., a discrepancy between different clock synchronizers such as food intake and light may uncouple peripheral tissue clocks from the SCN. Repeated intake of high-caloric food during the rest phase – the evening and night in humans, the day in nocturnal rodents – contributes to the development of obesity and disrupts endogenous circadian rhythms. Importantly, humans tend to consume palatable snacks mostly during the evening/the late active phase and mice are more vulnerable to palatable food overconsumption in the early rest phase.Chronic consumption of a palatable (hedonic) snack in the early rest phase in mice leads to increased body weight gain, disrupted metabolic circadian rhythms in body temperature, food intake, energy expenditure, and locomotor activity as well as increased assimilated energy during the first half of the rest phase. While it is known that the timing of snacking influences its metabolic effects and it is known that hedonic appetite rhythms critically depend on circadian clock function in dopaminergic neurons of the ventral tegmental area (VTA), it is unknown by which mechanisms timing affects the metabolic consequences of snacking. These mechanisms will be investigated in this proposed project. Our data so far support my hypothesis that the metabolic effects of timed chocolate snacking in the rest phase in mice depend on the integration of central (i.e., VTA) and peripheral (i.e., intestinal) time signals generated by respective circadian clocks. To dissect this interaction, I have three major objectives addressed in three work packages. In objective A, I will determine changes in daily transcriptome regulation in the small intestine and the VTA in male and female mice receiving a daily chocolate snack in the early rest phase. Additionally, microbiome samples will be analyzed in terms of rhythms and changed ratios in bacterial taxa upon snacking (WP1). In objectives B and C, I will investigate how function of the clock in VTA dopaminergic neurons (WP2) and how intestinal clock function (WP3) affects the metabolic and molecular consequences of chronic chocolate snacking in the rest phase. For objectives B and C mixed-sex cohorts will be used. Molecular readouts are focusing on daily transcriptome regulation in the small intestine and the VTA. Metabolic readouts will focus on body weight development, cumulative food intake, food intake rhythms and a daily profile of the assimilated energy. With this proposed project I will elucidate how the circadian clocks in the intestine and VTA dopaminergic neurons regulate the metabolic effects of a daily chocolate snack in the rest phase.

• DFG Programme: Research Grants