Current guidelines for the prevention and treatment of obesity focus on caloric restriction diets and increasing physical activity, but long-term compliance to these strategies is poor. The timing of meal intake relative to the light-dark and sleep-wake cycle is rarely considered in metabolic health; and modifying meal timing is likely easier to implement in daily life than reducing caloric intake and/or increasing physical activity. This project will test whether restricting the timing of energy intake to a short-defined period during wakefulness can be used to improve fuel utilization patterns and enhance circadian rhythms in metabolic tissues to optimize health.
Time restricted feeding (TRF; eating within \<10-h period followed by \>14-h fast) is a promising meal timing paradigm that in rodent studies improves multiple health indicators. When provided access to a high-fat diet ad libitum, mice rapidly gain weight. However, when fed the same diet under TRF conditions (food access restricted to an 8-h window during the active phase) mice appear to be protected from excessive weight gain and metabolic diseases. Preliminary studies in humans are showing improvements in 24-h glucose variability, fat oxidation, and blood pressure with TRF aligned to the early portion of the day compared to the ad libitum feeding schedule. A major research gap is whether the timing of the feeding window relative to sleep modifies metabolic responses. In a recent pilot and feasibility study incorporating TRF into a weight loss intervention the researchers asked participants to consume all food within a 10-h window to starting 1-h after waking for 12-weeks. The researchers' design choice was based on data showing that consuming energy in the evening is related to a two-fold increase in obesity risk. There also appears to be reduced weight loss effectiveness in dieters who consume the main meal later in the day. Some of the participants in the weight loss trial reported difficulty adhering to the early feeding schedule because it does not align well with social schedule (e.g., eating dinner with the family in the evening). Therefore, an important clinical question is whether late or mid-day TRF will result in similar metabolic benefits compared to the early TRF paradigm that has been tested in other studies. Additional rationale for studying early vs. late timed feeding is to address a fundamental question, "can timed meals shift the timing of metabolic rhythms?". Peripheral circadian clocks located in liver, adipose, and muscle tissue are sensitive to meal timing and control daily oscillations in fuel utilization and storage. A small study of 8 men demonstrated that a 5-h delay and meal timing was sufficient to delay the rhythmic expression of clock genes in white adipose tissue. Therefore, the investigators will leverage the design of the present study to examine the impact of meal timing on peripheral circadian rhythms in metabolism and their alignment to the sleep cycle.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
12
Consuming energy during a short interval during the day
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
Total fat oxidation in response to eTRF
Total fat oxidation will measured by whole room calorimetry. Early Time Restricted Feeding (eTRF) may occur at Week 1 or Week 5 depending on randomization.
Time frame: Week 1 or Week 5
Total fat oxidation in response to mTRF
Total fat oxidation will measured by whole room calorimetry. Mid-day Time Restricted Feeding (mTRF) may occur at Week 1 or Week 5 depending on randomization.
Time frame: Week 1 or Week 5
Insulin sensitivity in response to eTRF
Insulin sensitivity measured by three identical mixed meal tolerance tests administered across the day. Early Time Restricted Feeding (eTRF) may occur at Week 1 or Week 5 depending on randomization.
Time frame: Week 1 or Week 5
Insulin sensitivity in response to mTRF
Insulin sensitivity measured by three identical mixed meal tolerance tests administered across the day. Mid-day Time Restricted Feeding (mTRF) may occur at Week 1 or Week 5 depending on randomization.
Time frame: Week 1 or Week 5
Glucose control in response to eTRF
Glucose control will be measured by a continuous glucose monitor. Mid-day Time Restricted Feeding (mTRF) may occur at Week 1 or Week 5 depending on randomization.
Time frame: Week 1 or Week 5
Glucose control in response to mTRF
Glucose control will be measured by a continuous glucose monitor. Early Time Restricted Feeding (eTRF) may occur at Week 1 or Week 5 depending on randomization.
Time frame: Week 1 or Week 5
Difference in dietary fat oxidation between experimental conditions
Dietary fat oxidation will be measured using a stable isotope tracer
Time frame: Week 1 and Week 5
Difference in 24h energy expenditure between experimental conditions
24h energy expenditure will be measured using whole room calorimetry
Time frame: Week 1 and Week 5
Difference in sleep between experimental conditions
Sleep will be measured by polysomnography
Time frame: Week 1 and Week 5
Difference in the melatonin rhythm between experimental conditions
The melatonin profile will be measured in plasma during constant routine protocol
Time frame: Week 1 and Week 5
Difference in plasma metabolite rhythms between experimental conditions
Plasma metabolite rhythms will be measured using a constant routine protocol
Time frame: Week 1 and Week 5
Difference in plasma hormone rhythms between experimental conditions
Plasma hormone rhythms will be measured using a constant routine protocol
Time frame: Week 1 and Week 5
Difference in plasma gene expression rhythms between experimental conditions
Plasma gene expression rhythms will be measured using a constant routine protocol
Time frame: Week 1 and Week 5
Difference in energy expenditure rhythms between experimental conditions
Energy expenditure rhythms will be measured by indirect calorimetry during a constant routine protocol
Time frame: Week 1 and Week 5
Difference in substrate oxidation rhythms between experimental conditions
Substrate oxidation rhythms will be measured by indirect calorimetry during a constant routine protocol
Time frame: Week 1 and Week 5
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