Obesity
Conditions
Keywords
leptin, obesity
Brief summary
Our previous studies have demonstrated that there is substantial metabolic opposition to the maintenance of an altered body weight. Leptin is a protein secreted by fat cells and the circulating concentrations of leptin are directly proportional to fat mass. Leptin-deficiency is associated with severe obesity in rodents and in humans and the obesity is relieved by leptin administration. These studies examine the hypothesis that some of this metabolic opposition cto the maintenance of an altered body weight can be relieved by restoring circulating concentrations of the hormone leptin to the same range as at usual body weight in subjects who are maintaining a reduced body weight. The basic design of this study is to observe subjects at a 10% reduced body weight and then again at that reduced body weight while receiving physiological leptin or T3 supplementation.
Detailed description
We demonstrated a substantial metabolic resistance to maintenance of altered body weight. Leptin is secreted by fat cells in circulating concentrations that are directly proportional to fat mass. Leptin-deficiency is associated with severe obesity in rodents and in humans and the obesity is relieved by leptin administration. These studies examine the hypothesis that some of this metabolic opposition cto the maintenance of an altered body weight can be relieved by restoring circulating concentrations of the hormone leptin to the same range as at usual body weight in subjects who are maintaining a reduced body weight. The basic design of this study is to observe subjects at a 10% reduced body weight and then again at that reduced body weight while receiving physiological leptin or T3 supplementation.
Interventions
DRUGLeptin
leptin administration
BEHAVIORALDietary modification
Subjects lose 10% of body weight via dietary restriction
DRUGT3 repletion
administer T3
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
19 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Energy Expenditure (TEE) | At initial body weight; after 10% weight loss during placebo treatment; and after 10% weight loss during the 5-week repletion treatment period. | Total 24-hour energy expenditure was determined by caloric titration. At the reduced-weight repletion condition, TEE was calculated from weight-maintenance caloric intake adjusted for changes in body energy stores during the treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Resting Energy Expenditure (REE) | At initial body weight; after 10% weight loss during placebo treatment; and after 10% weight loss during the 5-week repletion treatment period. | Resting energy expenditure was measured by indirect calorimetry using a hood calorimeter at initial body weight, after 10% weight loss during placebo treatment, and after 10% weight loss during the repletion condition. |
| Non-Resting Energy Expenditure (NREE) | At initial body weight; after 10% weight loss during placebo treatment; and after 10% weight loss during the 5-week repletion treatment period. | Non-resting energy expenditure was calculated as total energy expenditure minus resting energy expenditure and the thermic effect of feeding: NREE = TEE - (REE + TEF). NREE was assessed at initial weight, after 10% weight loss during placebo treatment, and after 10% weight loss during the repletion condition. |
| Urinary Norepinephrine (24-hour Excretion) | Initial Wt; 10% Wt Loss + placebo; 10% Wt Loss + repletion | Urinary Norepinephrine (24-hour excretion) |
| Urinary Epinephrine (24-hour Excretion) | Initial Wt; 10% Wt Loss + Placebo; 10% Wt Loss + Repletion (5 weeks each condition) | 24-hour urinary epinephrine excretion measured at initial weight and after 10% weight loss during placebo and repletion conditions. |
Countries
United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 33.6 years STANDARD_DEVIATION 8.2 |
| % Body Fat | 43.1 percentage of body fat STANDARD_DEVIATION 11.6 |
| Diastolic Blood Pressure, mmHg | 68 mmHg STANDARD_DEVIATION 8 |
| Fat Free Mass (FFM), kg | 60.2 kg STANDARD_DEVIATION 13.6 |
| Fat Mass (FM), kg | 47.3 kg STANDARD_DEVIATION 21.3 |
| Leptin, ng/ml | 45.7 ng/ml STANDARD_DEVIATION 40.4 |
| Pulse, beats/minute | 72 bpm STANDARD_DEVIATION 8 |
| Region of Enrollment United States | 31 participants |
| Serum T3, ng/dl | 105.1 ng/dl |
| Serum T4, microg/dl | 6.89 microg/dl |
| Serum, thyroid-stimulating hormone (TSH) | 1.73 mU/l |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 3 Participants |
| Systolic Blood Pressure, mmHg | 113 mmHg STANDARD_DEVIATION 10 |
| T4/T3 ratio | 0.067 microgram/nanogram STANDARD_DEVIATION 0.015 |
| Temperature (Celsius) | 36.5 degrees STANDARD_DEVIATION 0.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
None listed