Biorhythms in Metabolic Tissues

Not Applicable

• Conditions: Biological Clocks; Sleep Deprivation; Metabolic Disturbance; Healthy

• Registration Number: NCT03276442
• Lead Sponsor: Uppsala University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-08-28
• Study Start: 2017-08-31
• Study First Submitted QC: 2017-09-07
• Study First Posted: 2017-09-08
• Status Verified: 2017-10
• Last Update Submitted: 2017-10-10
• Last Update Posted: 2017-10-12
• Primary Completion: 2019-11-30
• Study Completion: 2019-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Age 18-33 yr
• Healthy (self-reported) and not on medication
• BMI 18-28 kg/m2 (and waist circumference <102 cm), and weight stable (±5% body weight in past 6 months)
• Non-smoker and non-nicotine user
• Regular sleep-wake pattern, with sleep duration of 7-9.25 hrs per night
• Sedentary to moderately active with regular exercise habits the last 2 months
• Regular daily meal pattern with 3 main meals

Exclusion Criteria

• Major or chronic illness, e.g. diabetes, renal disease or inflammatory bowel disease
• Current or history of endocrine or metabolic disorders
• Psychiatric or neurological disorders (e.g. bipolar disorder, epilepsy)
• Frequent gastrointestinal symptoms
• Chronic medication
• Any sleep disorder (e.g. irregular bedtimes, symptoms of insomnia)
• Any issues with or allergies against the provided food items or utilized anesthesia
• Shift work in the preceding three months or for a long duration
• Time travel over two time zones in the preceding month
• Too much weight gain or weight loss in the preceding 6 months
• Pregnancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Changes in clock gene & associated omic circadian rhythms	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)	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

Secondary Outcome Measures

Name	Time	Method
Wakefulness-induced changes and subsequent recovery at omic levels	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	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
24-h rhythms in blood	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)	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
Diet-induced changes in gut microbiota and relation to circadian rhythms	Measured throughout study participation, i.e. on average over 6-7 weeks	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
Energy expenditure rhythms	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)	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
Urine metabolite rhythms	Measured throughout study participation, i.e. on average over 6-7 weeks	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
Rhythms of blood markers of damage to the central nervous system	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)	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
24-h rhythms in saliva	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)	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
Central circadian rhythms	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)	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

Trial Locations

Locations (1)

Department of Neuroscience, Uppsala University; 🇸🇪 Uppsala, Sweden