Effects of circadian misalignment and sleep disturbance on feeding patterns, obesity and the metabolic syndrome

The prevalence of obesity has increased worldwide to epidemic proportions. For
long-term treatment success permanent lifestyle changes are necessary with
regard to approach to food, physical activity patterns and behavior to
emotional stress. Until now, recommendations for improving food choice, food
intake patterns, and energy intake, as well as for normalizing physical
activity, have not resulted in solutions for prevention and treatment of
obesity. It may be that advices on the energy balance components energy intake
and energy expenditure lack the interaction with the subjects* individual
circadian alignment, or that circadian alignment is disturbed, due to
environmental pressure. Only one study till now has studied the consequences of
circadian misalignment in humans. Circadian misalignment, when subjects ate and
slept about 12h of phase from their habitual times, systematically decreased
leptin, increased glucose despite increased insulin, completely reversed the
daily cortisol rhythms, and increased arterial pressure. These findings
illustrate how circadian misalignment represents a high risk for overweight and
obesity.

The objective of the first part of the study is to assess whether circadian
misalignment:

- decreases energy expenditure and activity induced energy expenditure
- alters substrate oxidation
- alters feelings of hunger and satiety
- alters food choice and energy intake
- alters the reward system (wanting and liking)
- affects the endocrinological system
- alters body temperature
- alters sleep quality

Partly randomized single-blinded cross-over design.

Part I: subjects stay for each condition, for 3 circadian cycles, in the
absence of time cues, in a controlled situation under controlled energy balance
conditions in a respiration-chamber. In order to identify effects of circadian
misalignment and its associated sleep disturbance, subjects undergo randomly:
- circadian alignment by a 27 hrs light- and food-entrained cycle
- circadian misalignment by a 21 hrs light- and food-entrained cycle

The second part of the experiment will be conducted after completion of the
first part.

Part II: in order to assess two concepts of restoration of circadian
misalignment, the men first will be misaligned during a week at home, by a
short sleep duration, i.e. 6hrs sleep.
Each time thereafter they will follow the next two conditions in random order:
- 1 cycle of light-entrained circadian misalignment (21 hrs), followed by two
cycles of light-entrained circadian re-alignment (27 hrs), with a feeding
schedule on demand
- 1 cycle of light-entrained circadian misalignment (21 hrs), followed by two
cycles of food-entrained circadian re-alignment (27 hrs), under dim light
conditions of 1.8 lux.

During all testdays, subjects will stay time blinded in the respiration chamber
to measure energy expenditure, substrate oxidation and physical activity,
during three light-entrained circadian cycles of a 1:2 ratio. A short cycle
will be 21 hrs (7/14), a long cycle 27 hrs (9/18). Light-entrainment will be
achieved using day-light lamps during the waking hours and black-out curtains
during the sleeping hours. During food-entrainment, light conditions will be
dim light continuously, (about 1.8 lux), to minimize any light-entrained
influence on the circadian system. During their stay in the chamber, subjects
will be fed in energy balance in a food-entrained way, at time-points related
to their cycle duration. EEG will be used to measure wake and sleep phases
continuously. Heart rate will be monitored using a ECG and body temperature
using a CorTemp* Data Recorder (HQInc., Palmetto (FL), USA). Appetite and
mood profiles will be measured hourly and before and after each meal, by
anchored 100 mm visual analogue scales and by POMS and STAI-state
questionnaires. Also, the blood-parameters will be measured hourly, and growth
hormone will be measured every 20 minutes. Finally, effects of on food reward
and energy intake will be measured by means of a validated wanting and liking
computer-test, before and during the evening meal before subjects leave the
chamber. This evening meal consists of subjects* food choice, and will be given
ad libitum. Food choice, rewarding characteristics, macronutrient composition,
energy-density, and energy content will be calculated.

This study does not include any major risks for the subjects. During the
time-blinded two researchers will always be present during the subjects stay in
the respiration chamber. There are no risks for the subjects in using any of
the meals because people with certain food allergies are excluded and all
products are regular food items available at the local supermarket (AH). The
*thermometer pill* that they have to swallow is completely harmless and runs
through the digestive system, where it eventually will exit the body via the
feces. Blood sampling in this study is limited and without side effects, apart
from its usual risks of minor bruising. Urine sampling is done in urine bottles
with 10 ml of diluted HCl, which might pose a risk for the subjects, however
they will be carefully instructed on how to sample the urine and handle the
urine bottles. The subject does needs to follow our schedule on sleeping,
filling in questionnaires and eating, however, the majority of the time the
subject is awake he can fill in his own time. The experiment will cost about
144 hours of the subject*s time.