Timing of Eating Study Among Obese Adults

The study consists of the following phases - screening, assessment visit 1, eating condition
1, assessment visit 2, a wash-out period, assessment visit 3, eating condition 2 and
assessment visit 4, as discussed in detail below. The assessment visits will all consist of
the same procedures and will take place at the Center for Human Phenomic Science (CHPS) of
the Hospital of the University of Pennsylvania before and after each of the eating conditions
(four times total). The four 28-hour inpatient assessments will consist of blood draws,
adipose (fat) tissue sampling, a dual energy X-ray absorptiometry (DEXA) scan, and a resting
metabolic rate test.

During the screening period in order to determine eligibility, participants must complete a
2-part screening visit; This includes:

1. A complete physical examination

2. Tests of blood to screen for any conditions such as diabetes or any serious,
uncontrolled medical condition that may interfere with participation in the study.

3. An Electrocardiogram (EKG) test

4. Urine Pregnancy Test

5. Urine Drug Screening

6. the completion of several self-report questionnaires and structured interviews

During the screening period, participants will also be asked to keep a 10-day food log where
they will record all food and beverages consumed and their sleep and exercise schedule.
Participants will be asked to wear an Actigraph wrist watch at this time.

Following successful completion of the screening period, participants will complete the first
of 4 assessment visits. All assessment visits will follow the same protocol.

Assessment Visit Day 1 Procedures:

The visit will include 28 hours (overnight) spent at the CHPS, where meals and snacks will be
provided. At each of the assessment visits participants will be given a urine drug screening
and, if appropriate, a pregnancy test. The lights will be dim in the hospital room to control
for light.

Participants will arrive at 7:00 am. Starting at 8:00 am, blood will be drawn every four
hours. From this blood gene expression and hormones related to metabolism, eating, and sleep
will be measured.

Following the first blood draw, resting metabolic rate is measured for 45 minutes. Lunch is
then provided, followed by a measurement of body composition using a DEXA scan. Next, the
adipose tissue sampling procedure will begin.

Participants will be provided meals and snacks during their visit and are free to watch
television or participate in other sedentary pastimes while they are there.

Assessment Visit Day 2 Procedures:

After an overnight fast, participants will undergo the Frequently Sampled Intravenous Glucose
Tolerance Test (FSIGT) on the morning of day 2.

Following the FSIGT test, participants will be served a meal and during the first assessment
visit, participants will be randomly assigned to start with one of two eating conditions for
the next 8 weeks: 1) Daytime or 2) Delayed. Following randomization, participants will be
discharged from CHPS and begin eating condition 1.

If participants are assigned to the daytime eating condition first, they will be asked to
consume all of their meals and snacks each day between 8:00 am and 7:00 pm. If they are
assigned to the delayed eating condition first, they will be asked to consume all of their
meals and snacks between 12 noon and 11:00 pm each day. Participants will eat on this
schedule for 8 weeks. During the two, 8-week eating periods, all of the meals and snacks will
be provided by the research kitchen. During the eating conditions, participants will be asked
to complete daily self-report queries concerning their adherence to the food, sleep, and
physical activity requirements of the study.

Following eating condition 1, participants will return for assessment visit 2. This
assessment visit follows the same procedures as all other assessment visits. Following
assessment visit 2, participants will begin their 2 week washout period where they are
instructed to eat as they normally would whenever they like. Following the two-week washout
period, participants will return for assessment visit 3, after which they will begin eating
condition 2. Following 8 weeks of eating condition 2 participants will return for their final
visit, assessment visit 4. After this final assessment, participation in the study will be
complete.

Inclusion Criteria:

- age 21-50

- BMI of 30-50 kg/m2

- stable weight (±10 lb) over the previous 6 months

- women must be pre-menopausal with regular menstrual cycles

Exclusion Criteria:

- unstable, serious medical conditions

- use of medicine linked to weight gain/loss

- metabolic syndrome

- cardiac conditions

- cancer

- diabetes

- autoimmune disease

- use of illicit drugs, melatonin, diuretics or hypnotics

- involved in a current weight loss program

- presence of a sleep disorder (determined by surveys and actigraphy)

- those who work shift work

- those with extreme chronotypes

- habitual waking outside of 0600h-0930h

- habitual bedtime <2200h or >2400h

- sleep duration of <6.5 or >8.5 h/night.

- psychiatric exclusions will be: depression (Patient Health Questionnaire-9 score ≥9),
lifetime bipolar disorder, psychosis, or eating disorder; or any other severe
psychiatric disorder judged to interfere with study adherence as assessed by the MINI
International Neuropsychiatric Interview.

- structured exercise >3 d/wk, for >30 min measured by exercise logs and actigraphy;
normal activity levels are required during the study (±30 min/wk of baseline level).