Biological Rhythms in Metabolic Tissues: Impact of Diet
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- Enrollment
- 12
- Locations
- 2
- Primary Endpoint
- Changes in clock gene & associated omic circadian rhythms
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- None
Masking Description
In the crossover subgroup condition, participants will not be briefed about what diet they will receive before the actual onset of the dietary intervention
Eligibility Criteria
- Ages
- 18 Years to 32 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
Healthy diet
'Low-fat dietary intervention' to be administered to participants
Intervention: Low-fat dietary intervention (Other)
Unhealthy diet
'High-fat dietary intervention' to be administered to participants
Intervention: High-fat dietary intervention (Other)
Outcomes
Primary Outcomes
Changes in clock gene & associated omic circadian rhythms
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)
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 Outcomes
- 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)
- 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))
- Diet-induced changes in gut microbiota and relation to circadian rhythms(Measured throughout study participation, i.e. on average over 6-7 weeks)
- 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))
- Urine metabolite rhythms(Measured throughout study participation, i.e. on average over 6-7 weeks)
- 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))
- 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))
- 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))