Peripheral tissues (e.g. liver, adipose, muscle) express self-sustained circadian clocks that coordinate daily metabolic rhythms. The timing of clock rhythms in peripheral tissues is highly sensitive to feeding-fasting signals across the sleep-wake transition. Nutritional insults such as high fat overfeeding (HF-OF) have been shown to attenuate clock gene expression in peripheral tissues resulting in a deleterious re-programming of the circadian metabolome. Studies in humans have only superficially investigated how the circadian clock machinery is impacted by nutritional signals. The overall goal of this pilot project is to take the first steps toward developing translational methods to investigate links between changes in energy flux and the circadian system in human tissues. Using an innovative ex vivo cell culture approach the investigators will examine the impact of 3-days of HF-OF compared to eucaloric (EU) feeding on the expression of core clock genes in human subcutaneous adipose tissue (SAT). The Investigators hypothesize that compared to EU, the amplitude of clock gene expression in SAT measured over 24hrs will be attenuated following short-term HF-OF. This pilot project will serve as a launch point for designing future studies into the effects of diet and exercise on the circadian control of metabolism in adipose tissue depots as well as other tissues (e.g. muscle).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
10
3 days of a diet designed to maintain energy balance
3 days of a diet designed to induce a 40% positive energy balance
Unnamed facility
Denver, Colorado, United States
Expression of clock genes in adipose tissue.
Gene expression measured at two time points from abdominal fat.
Time frame: Measured through study completion, an average of 4 weeks.
Gene expression of key cellular fuel sensors thought to be controlled. and/or influenced by peripheral clocks
Gene expression measured at two time points from abdominal fat.
Time frame: Measured through study completion, an average of 4 weeks.
Expression of clock genes in blood monocytes.
Gene expression measured at two time points from abdominal fat.
Time frame: Measured through study completion, an average of 4 weeks.
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