Energy Expenditure and Weight Loss Maintenance

Participants were recruited in three groups: weight loss maintainers (WLM: maintaining ≥13.6
kg weight loss for ≥1 year), normal weight controls (NC: Body Mass Index (BMI) matched to
current BMI of WLM), and controls with overweight/obesity (Overweight Controls (OC): BMI
matched to pre-weight loss maximum BMI of WLM). The investigators hypothesize that total
daily energy expenditure (TDEE) in WLM is similar to OC but is significantly higher then NC.
High levels of volitional physical activity may compensate for the reduction in energy
expenditure ("energy gap") that is the expected result of weight loss. This allows WLM to
maintain a high level of "energy flux", which may facilitate optimal body weight regulation
over time. The investigators will use doubly labeled water to compare TDEE in WLM and both NC
and OC. The investigators will also compare individual components of TDEE including resting
energy expenditure (REE), thermic effect of food (TEF), physical activity energy expenditure
(PAEE), and physical activity level (PAL) between groups. The investigators also hypothesize
that REE in WLM is similar to controls of both types under free living conditions, but will
decrease following a period of physical inactivity and be significantly less than controls.
Studies in rodents have consistently shown evidence of an increase in metabolic efficiency in
the reduced obese state manifested by a lower than predicted REE. Studies in humans have
shown mixed results, however few studies have controlled for habitual level of physical
activity. Recent evidence suggests REE is greater in adults who perform regular exercise than
their sedentary peers; this difference can be attributed in part to greater tonic sympathetic
nervous system stimulation of REE that occurs in habitually exercising adults. The
investigators believe there is an increase in metabolic efficiency in the reduced obese state
manifested by a lower than predicted REE, and that high levels of physical activity function
to "mask" or "correct" this metabolic efficiency. The investigators will compare REE under
free living conditions and during an experimentally imposed period of reduced energy flux
(restricted physical activity matched by an equivalent reduction in energy intake) in WLM and
controls.

Inclusion Criteria:

- Men or women

- Age 18-65

- Weight stable (<10 lb fluctuation in body weight over previous 6 months) or

- NWCR subjects successful at weight loss maintenance (maintaining a loss of ≥ 30 pounds
for at least 2 years)

- Non-Reduced Weight Matched Controls: Individuals matched to NWCR subjects' current
body weight. These individuals will be normal weight (BMI 18-25, BMI up to 27 allowed
in men with waist circumference < 40 cm), and have no history of overweight or obesity
(BMI >25) and will not be maintaining a weight loss ≥ 30 pounds.

- Non-Reduced Obese Controls: Individuals matched to NWCR subjects' maximum pre-weight
loss body weight. These individuals will be overweight or obese (BMI ≥ 26-45).

Exclusion Criteria:

- Diabetes

- Uncontrolled HTN (>160/100)

- History of cardiac disease: CHF or angina, atrial fibrillation or ventricular
tachycardia, or significant abnormality on resting EKG

- Symptoms suggestive of cardiovascular disease: chest pain, shortness of breath at rest
or with mild exertion, dizziness, syncope.

- History of neurological disease: stroke, TIA or seizure disorder

- Current treatment for cancer (except skin)

- Severe pulmonary, liver or kidney disease

- Untreated thyroid disorder

- Severe arthritis or other musculoskeletal disorder

- Alcohol or drug abuse

- Active psychiatric illness

- Positive response to PAR-Q indicating requirement for monitored physical activity

- Other serious medical condition as determined by the investigator which would limit
physical activity or require monitored activity.

- Pregnant and lactating women, and women actively trying to become pregnant
(post-menopausal women on a stable dose of HRT and pre-menopausal women on a stable
OCP regimen will be allowed to participate)

- Smoking within the past 6 months

- Subjects using prescription or over the counter medication which may affect RMR
including beta blockers, stimulants such as Ritalin and appetite suppressants.

- Subjects who have undergone bariatric surgery or who are currently maintaining their
weight loss with prescription weight loss drugs or supplements.

- Severe claustrophobia

- Moderate or high levels of physical activity at the workplace and unable to reduce
workplace activity, work from home or take time off from work to participate in Study
2.

- We will exclude controls if they are weight reduced (maintaining a weight loss of ≥ 30
pounds).