Metabolism is increasingly recognized as being highly regulated by anticipatory biological rhythms (circadian rhythms or "biorhythms"), which are driven by molecular feedback loops, and which are approximately 24 hours long ("circa diem"). These circadian rhythms exist both centrally, in the brain, but also in the periphery, and are specific to many tissues depending on their main biological function or functions. Whereas these circadian rhythms have been thoroughly characterized in other organisms, their role in humans remain poorly understood, partly because of the difficulty in studying these rhythms in peripheral tissues. The investigators therefore aim to characterize these rhythms in primarily skeletal muscle and adipose tissue in healthy young volunteers (using the so-called constant routine paradigm), and how these rhythms interact with one another at various genetic and molecular levels. At the same time, the investigators aim to study how an unhealthy vs. healthy diet can alter these circadian rhythms, and how they interact with circadian rhythms in other tissue compartments such as those expressed by blood cells.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
12
Low-fat diet (5-7 days) preceding extended wakefulness under standardized conditions
High-fat diet (5-7 days) preceding extended wakefulness under standardized conditions
Department of Neuroscience, Uppsala University
Uppsala, Sweden
RECRUITINGChanges in clock gene & associated omic circadian rhythms
Changes in clock gene \& associated clock-regulated \& clock-independent metabolic and omic circadian rhythms (e.g. in epigenome, transcriptome, metabolites) in peripheral tissues (primarily skeletal muscle and adipose tissue), and interplay between these rhythms across the 24-h period and under the different dietary conditions
Time frame: Measured repeatedly (every 6 hours for 24 hours) during a period of extended wakefulness, following each dietary intervention (i.e. over a total period of 6-7 weeks)
Wakefulness-induced changes and subsequent recovery at omic levels
Changes at omic levels (e.g. DNA methylation, transcriptome, proteome, metabolome) in peripheral tissues (primarily skeletal muscle and adipose tissue), urine and feces samples due to extended wakefulness following subsequent recovery, following each dietary intervention
Time frame: Following each dietary intervention (i.e. over a total period of 6-7 weeks), measured repeatedly (every 2-6 hours for 24 hours) during a period of extended wakefulness, and after recovery sleep
24-h rhythms in blood
Changes in rhythms in blood-borne cells, proteins and other molecular factors such as DNA, hormones, and proteins, due to the preceding dietary intervention, and relation to other rhythms measured across 24 hrs following the two dietary conditions
Time frame: Measured repeatedly (every 2-3 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)
Diet-induced changes in gut microbiota and relation to circadian rhythms
Changes in gut microbiota (metagenomic, compositional) due to dietary intervention, and relation to circadian rhythms measured across 24 hrs in peripheral tissues following the two dietary conditions
Time frame: Measured throughout study participation, i.e. on average over 6-7 weeks
Energy expenditure rhythms
Changes in energy expenditure rhythms due to the preceding dietary intervention, and relation to other rhythms measured across 24 hrs following the two dietary conditions
Time frame: Measured repeatedly (every 2 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)
Urine metabolite rhythms
Changes in levels of urine metabolites due to dietary intervention, and relation to circadian rhythms across 24 hrs in peripheral tissues following the two dietary conditions
Time frame: Measured throughout study participation, i.e. on average over 6-7 weeks
Rhythms of blood markers of damage to the central nervous system
Assessment of rhythms in of blood markers of damage to the central nervous system (e.g. Olink Proseek multiplex panel, neuron-specific enolase, S-100b) across a 24-h period and following subsequent recovery sleep, following the two dietary conditions
Time frame: Measured repeatedly (every 1-3 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)
24-h rhythms in saliva
Changes in rhythms in saliva-borne cells, proteins and other molecular factors such as DNA, hormones, and proteins, due to the preceding dietary intervention, and relation to other rhythms measured across 24 hrs following the two dietary conditions
Time frame: Measured repeatedly (every 2-3 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)
Central circadian rhythms
Changes in centrally driven circadian rhythms (e.g. temperature and melatonin), due to the preceding dietary intervention, and relation to other rhythms measured across 24 hrs following the two dietary conditions
Time frame: Measured repeatedly (every 1-3 hours over 24 hours) during a period of extended wakefulness and after subsequent recovery, following each dietary intervention (i.e. over a total period of 6-7 weeks)
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