Thyroid and Fat Tissue Metabolism
| Status: | Completed |
|---|---|
| Conditions: | Healthy Studies |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 10/8/2017 |
| Start Date: | April 3, 2006 |
| End Date: | July 8, 2014 |
Thyroid Hormone-Induced Lipolysis: An In Vivo Microdialysis Study
This study will use a technique called microperfusion to examine how thyroid hormones are
involved in fat metabolism. The thyroid gland produces two kinds of hormones: T3 and T4. Some
of the T4 is changed to T3 in various organs after leaving the thyroid. The T3 stimulates the
body to burn fat. People have different rates at which they can change T4 to T3, and this may
lead to differences in body fat among different people.
Microperfusion is based on the exchange of substances across tiny holes of a small plastic
tube called a "probe," which is inserted after numbing the skin over a fat pad. Through these
openings, the fat pad is continuously rinsed with small amounts of fluid, and an exchange of
substances occurs. The fluid drips from the other opening of the probe and is collected in a
vial. Small amounts of study drugs are infused and the amount of substances released by the
fat pad in response to them are measured.
Healthy normal volunteers 18 years of age and older may be eligible for this study.
Candidates are screened with a medical history, physical examination and blood tests.
Participants undergo microperfusion. A needle is placed in an arm vein for collecting blood
samples before and at the end of the experiment for measuring thyroid hormones and other
substances in the blood. The skin over the fat pad next to the umbilicus (navel) is numbed
and two microperfusion probes are inserted. A salt water solution is infused into the fat pad
for one hour and the substances in the fluid are measured as the fluid leaves the fat pad.
After 1 hour isoproterenol, a drug that aids in energy production by fat, is added to help
determine the level of fat metabolism. After an additional hour small amounts of thyroid
hormone are added to the fluid and samples are collected as they leave the body. Two
catheters are inserted during each experiment. Small volumes of sterile fluid are circulated
continuously in the tubing and samples are collected at regular intervals.
involved in fat metabolism. The thyroid gland produces two kinds of hormones: T3 and T4. Some
of the T4 is changed to T3 in various organs after leaving the thyroid. The T3 stimulates the
body to burn fat. People have different rates at which they can change T4 to T3, and this may
lead to differences in body fat among different people.
Microperfusion is based on the exchange of substances across tiny holes of a small plastic
tube called a "probe," which is inserted after numbing the skin over a fat pad. Through these
openings, the fat pad is continuously rinsed with small amounts of fluid, and an exchange of
substances occurs. The fluid drips from the other opening of the probe and is collected in a
vial. Small amounts of study drugs are infused and the amount of substances released by the
fat pad in response to them are measured.
Healthy normal volunteers 18 years of age and older may be eligible for this study.
Candidates are screened with a medical history, physical examination and blood tests.
Participants undergo microperfusion. A needle is placed in an arm vein for collecting blood
samples before and at the end of the experiment for measuring thyroid hormones and other
substances in the blood. The skin over the fat pad next to the umbilicus (navel) is numbed
and two microperfusion probes are inserted. A salt water solution is infused into the fat pad
for one hour and the substances in the fluid are measured as the fluid leaves the fat pad.
After 1 hour isoproterenol, a drug that aids in energy production by fat, is added to help
determine the level of fat metabolism. After an additional hour small amounts of thyroid
hormone are added to the fluid and samples are collected as they leave the body. Two
catheters are inserted during each experiment. Small volumes of sterile fluid are circulated
continuously in the tubing and samples are collected at regular intervals.
This study will examine how two thyroid preparations, levothyroxine (T4) and liothyronine
(T3), affect subcutaneous adipose tissue in normal subjects. Thyroid hormone plays an
important role in the maintenance of energy metabolism. Specifically, hyperthyroidism is
associated with weight loss via an increase in metabolic rate and lipolysis. While this
phenomenon has been studied in vitro quite extensively, very little information is available
on the local action of thyroid hormone on adipose tissue in vivo and, in particular, at the
present no information is available on the role of peripheral conversion of thyroid hormone
in subcutaneous adipose tissue. We thus propose to study the local action of thyroid hormones
on adipose tissue using microdialysis, a minimally invasive technique that allows the serial
determination of components of the extracellular fluid. The measurement of glycerol after
correction for changes in blood flow will be used to evaluate the effects of the thyroid
hormones on local lipolysis.
Healthy volunteers 18 years of age and older may be eligible for this study. Candidates are
screened with a medical history, physical examination, and blood tests. Subjects with
hyperlipidemia, impaired glucose tolerance or diabetes and thyroid disease are not eligible
for the participation in this study. Qualifying study participants undergo subcutaneous fat
tissue microdialysis to assess the effects of T3 and T4 on the activity of fat tissue. The
medications isoproterenol and T3 or T4 are injected in fat tissue under the skin of the
abdomen, and fluid samples are collected from the area over a 6-12 hour period using the same
small needle. Glycerol is then measured to study how the thyroid hormones affect fat
metabolism. During this procedure a 10% glucose solution is infused through the catheter in
the arm to limit lipolysis due to fasting. Four different sets of experiments are performed
with different thyroid hormone doses and/or durations.
These experiments will provide new information on the role of thyroid hormone in the
regulation of adipose tissue metabolism and will help in identifying new treatments for the
management of obesity.
(T3), affect subcutaneous adipose tissue in normal subjects. Thyroid hormone plays an
important role in the maintenance of energy metabolism. Specifically, hyperthyroidism is
associated with weight loss via an increase in metabolic rate and lipolysis. While this
phenomenon has been studied in vitro quite extensively, very little information is available
on the local action of thyroid hormone on adipose tissue in vivo and, in particular, at the
present no information is available on the role of peripheral conversion of thyroid hormone
in subcutaneous adipose tissue. We thus propose to study the local action of thyroid hormones
on adipose tissue using microdialysis, a minimally invasive technique that allows the serial
determination of components of the extracellular fluid. The measurement of glycerol after
correction for changes in blood flow will be used to evaluate the effects of the thyroid
hormones on local lipolysis.
Healthy volunteers 18 years of age and older may be eligible for this study. Candidates are
screened with a medical history, physical examination, and blood tests. Subjects with
hyperlipidemia, impaired glucose tolerance or diabetes and thyroid disease are not eligible
for the participation in this study. Qualifying study participants undergo subcutaneous fat
tissue microdialysis to assess the effects of T3 and T4 on the activity of fat tissue. The
medications isoproterenol and T3 or T4 are injected in fat tissue under the skin of the
abdomen, and fluid samples are collected from the area over a 6-12 hour period using the same
small needle. Glycerol is then measured to study how the thyroid hormones affect fat
metabolism. During this procedure a 10% glucose solution is infused through the catheter in
the arm to limit lipolysis due to fasting. Four different sets of experiments are performed
with different thyroid hormone doses and/or durations.
These experiments will provide new information on the role of thyroid hormone in the
regulation of adipose tissue metabolism and will help in identifying new treatments for the
management of obesity.
- INCLUSION CRITERIA:
- Age greater than or equal to 18 years, male or female.
- Written informed consent.
EXCLUSION CRITERIA:
- Hypo- or hyper-thyroid (history or TSH greater than 5.0 and less than 0.4 miU/L)
- Blood pressure greater than 140/90 mmHg [17] or current antihypertensive therapy
- History of cardiovascular disease
- BMI less than or equal to 20 or greater than or equal to 30 Kg/m(2).
- Diabetes mellitus (serum glucose greater than or equal to 126 mg/dL).
- Hypercholesterolemia (serum levels greater than or equal to 240 mg/dL),
hypertriglyceridemia (plasma levels greater than or equal to 220 mg/dL) and/or use of
antilipemic therapy.
- Liver disease or ALT serum level greater than two fold the upper laboratory reference
limit.
- Renal insufficiency or estimated creatinine clearance less than or equal to 50 mL/min
(Cockcroft method).
- History of illicit drug or alcohol abuse within the last 5 years; current use of drugs
(by history) or alcohol (CAGE greater than 3).
- Psychiatric conditions or behavior that would be incompatible with safe and successful
participation in this study
- Current use of medications/dietary supplements/alternative therapies known to alter
thyroid function.
- Allergy to ethanol, levothyroxine, liothyronine, isoproterenol, lidocaine.
- Pregnancy/breastfeeding.
- Current smoker
All subjects will be fully informed of the aim, nature, and risks of the study prior to
giving written informed consent.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Click here to add this to my saved trials
