Thyroid Hormones Homeostasis and Energy Metabolism Changes During Stimulation of Endogenously Secreted Bile Acids (BAs)
| Status: | Completed |
|---|---|
| Conditions: | Healthy Studies, Obesity Weight Loss |
| Therapuetic Areas: | Endocrinology, Other |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 10/21/2017 |
| Start Date: | June 23, 2008 |
| End Date: | August 21, 2012 |
Postprandial thermogenesis, or thermic effect of food are terms that describe the increase in
utilization of energy by the human body following a meal. The mechanisms involved in this
process are believed to differ according to the type of food consumed, whether fat, protein
or carbohydrate.
The bile acids (BAs), unique substances secreted by the gall bladder into the gut after a
meal, play an important role in the absorption of fat and the management of cholesterol
stores in the body. Recent studies suggest that BAs may also serve as regulators of energy
expenditure (consumption) in the cells of our body by increasing the production of T3, an
active form of thyroid hormone. T3 in turn is believed to increase the efficiency with which
our bodies burn calories thereby generating heat. Although this process has been shown to be
effective in rodents who demonstrated weight loss after treatment, the role of BAs in humans
is poorly understood. Thus we do not know whether endogenous (produced by the body) or
exogenous (taken as medication) BAs play a significant role in the maintenance of body
weight. We hypothesize that, similarly to rodents, humans will respond to BAs by increasing
energy expenditure via the production of the active form of thyroid hormone.
This randomized, cross-over study will look at changes in thyroid hormones and energy
consumption in response to stimuli of endogenous BA secretion including dietary content, and
to the intake of pharmacological doses of bile acids.
Following a two-day period of equilibration diet, 30 healthy volunteers will be randomly
assigned to receive either a high-fat or high-carbohydrate isocaloric meal followed by a
6-hour metabolic chamber stay; the next day they will be crossed-over to the alternate
intervention. During the following three days, the study subjects will again be randomized to
receive either an intravenous injection of sincalide (the C-terminal octapeptide fragment of
cholecystokinin) 0.04 mcg/kg or placebo and P.O. placebo, or I.V. placebo and 15 mg/kg of BA
(ursodiol) with similar metabolic chamber stays and cross-over design.
The following parameters will be recorded and compared to placebo:
Energy expenditure
Substrate utilization
Spontaneous movements
Skin and core temperature
Serial changes in circulating thyroid hormones
Serial changes in bile acid serum concentrations
The data gathered from this study will provide greater insight into the physiological and
molecular mechanism(s) regulating the relation between endogenous bile acid secretion and
energy metabolism in response to meals, as well as the role of BAs per se on energy
metabolism.
utilization of energy by the human body following a meal. The mechanisms involved in this
process are believed to differ according to the type of food consumed, whether fat, protein
or carbohydrate.
The bile acids (BAs), unique substances secreted by the gall bladder into the gut after a
meal, play an important role in the absorption of fat and the management of cholesterol
stores in the body. Recent studies suggest that BAs may also serve as regulators of energy
expenditure (consumption) in the cells of our body by increasing the production of T3, an
active form of thyroid hormone. T3 in turn is believed to increase the efficiency with which
our bodies burn calories thereby generating heat. Although this process has been shown to be
effective in rodents who demonstrated weight loss after treatment, the role of BAs in humans
is poorly understood. Thus we do not know whether endogenous (produced by the body) or
exogenous (taken as medication) BAs play a significant role in the maintenance of body
weight. We hypothesize that, similarly to rodents, humans will respond to BAs by increasing
energy expenditure via the production of the active form of thyroid hormone.
This randomized, cross-over study will look at changes in thyroid hormones and energy
consumption in response to stimuli of endogenous BA secretion including dietary content, and
to the intake of pharmacological doses of bile acids.
Following a two-day period of equilibration diet, 30 healthy volunteers will be randomly
assigned to receive either a high-fat or high-carbohydrate isocaloric meal followed by a
6-hour metabolic chamber stay; the next day they will be crossed-over to the alternate
intervention. During the following three days, the study subjects will again be randomized to
receive either an intravenous injection of sincalide (the C-terminal octapeptide fragment of
cholecystokinin) 0.04 mcg/kg or placebo and P.O. placebo, or I.V. placebo and 15 mg/kg of BA
(ursodiol) with similar metabolic chamber stays and cross-over design.
The following parameters will be recorded and compared to placebo:
Energy expenditure
Substrate utilization
Spontaneous movements
Skin and core temperature
Serial changes in circulating thyroid hormones
Serial changes in bile acid serum concentrations
The data gathered from this study will provide greater insight into the physiological and
molecular mechanism(s) regulating the relation between endogenous bile acid secretion and
energy metabolism in response to meals, as well as the role of BAs per se on energy
metabolism.
Postprandial thermogenesis, or thermic effect of food are terms that describe the increase in
utilization of energy by the human body following a meal. The mechanisms involved in this
process are believed to differ according to the type of food consumed, whether fat, protein
or carbohydrate.
The bile acids (BAs), unique substances secreted by the gall bladder into the gut after a
meal, play an important role in the absorption of fat and the management of cholesterol
stores in the body. Recent studies suggest that BAs may also serve as regulators of energy
expenditure (consumption) in the cells of our body by increasing the production of T3, an
active form of thyroid hormone. T3 in turn is believed to increase the efficiency with which
our bodies burn calories thereby generating heat. Although this process has been shown to be
effective in rodents who demonstrated weight loss after treatment, the role of BAs in humans
is poorly understood. Thus we do not know whether endogenous (produced by the body) or
exogenous (taken as medication) BAs play a significant role in the maintenance of body
weight. We hypothesize that, similarly to rodents, humans will respond to BAs by increasing
energy expenditure via the production of the active form of thyroid hormone.
This randomized, cross-over study will look at changes in thyroid hormones and energy
consumption in response to stimuli of endogenous BA secretion including dietary content, and
to the intake of pharmacological doses of bile acids.
Following a two-day period of equilibration diet, 30 healthy volunteers will be randomly
assigned to receive either a high-fat or high-carbohydrate isocaloric meal followed by a
6-hour metabolic chamber stay; the next day they will be crossed-over to the alternate
intervention. During the following three days, the study subjects will again be randomized to
receive either an intravenous injection of sincalide (the C-terminal octapeptide fragment of
cholecystokinin) 0.04 mcg/kg or placebo and P.O. placebo, or I.V. placebo and 15 mg/kg of BA
(ursodiol) with similar metabolic chamber stays and cross-over design.
The following parameters will be recorded and compared to placebo:
Energy expenditure
Substrate utilization
Spontaneous movements
Skin and core temperature
Serial changes in circulating thyroid hormones
Serial changes in bile acid serum concentrations
The data gathered from this study will provide greater insight into the physiological and
molecular mechanism(s) regulating the relation between endogenous bile acid secretion and
energy metabolism in response to meals, as well as the role of BAs per se on energy
metabolism.
utilization of energy by the human body following a meal. The mechanisms involved in this
process are believed to differ according to the type of food consumed, whether fat, protein
or carbohydrate.
The bile acids (BAs), unique substances secreted by the gall bladder into the gut after a
meal, play an important role in the absorption of fat and the management of cholesterol
stores in the body. Recent studies suggest that BAs may also serve as regulators of energy
expenditure (consumption) in the cells of our body by increasing the production of T3, an
active form of thyroid hormone. T3 in turn is believed to increase the efficiency with which
our bodies burn calories thereby generating heat. Although this process has been shown to be
effective in rodents who demonstrated weight loss after treatment, the role of BAs in humans
is poorly understood. Thus we do not know whether endogenous (produced by the body) or
exogenous (taken as medication) BAs play a significant role in the maintenance of body
weight. We hypothesize that, similarly to rodents, humans will respond to BAs by increasing
energy expenditure via the production of the active form of thyroid hormone.
This randomized, cross-over study will look at changes in thyroid hormones and energy
consumption in response to stimuli of endogenous BA secretion including dietary content, and
to the intake of pharmacological doses of bile acids.
Following a two-day period of equilibration diet, 30 healthy volunteers will be randomly
assigned to receive either a high-fat or high-carbohydrate isocaloric meal followed by a
6-hour metabolic chamber stay; the next day they will be crossed-over to the alternate
intervention. During the following three days, the study subjects will again be randomized to
receive either an intravenous injection of sincalide (the C-terminal octapeptide fragment of
cholecystokinin) 0.04 mcg/kg or placebo and P.O. placebo, or I.V. placebo and 15 mg/kg of BA
(ursodiol) with similar metabolic chamber stays and cross-over design.
The following parameters will be recorded and compared to placebo:
Energy expenditure
Substrate utilization
Spontaneous movements
Skin and core temperature
Serial changes in circulating thyroid hormones
Serial changes in bile acid serum concentrations
The data gathered from this study will provide greater insight into the physiological and
molecular mechanism(s) regulating the relation between endogenous bile acid secretion and
energy metabolism in response to meals, as well as the role of BAs per se on energy
metabolism.
- INCLUSION CRITERIA:
Age greater than or equal to18 years, male or female
Written informed consent
EXCLUSION CRITERIA:
Hypo- or hyperthyroidism (history or serum TSH greater than 5.0 or less than 0.4 miU/L)
Blood pressure greater than 140/90 mmHg (26) or receiving antihypertensive therapy
History of cardiovascular disease
BMI less than or equal to 20 or greater than or equal to 27 Kg/m(2)
Diabetes mellitus (fasting serum glucose greater than or equal to 126 mg/dL)
Hyperlipidemia (serum total cholesterol greater than or equal to 240 mg/dL, triglycerides
greater than or equal to 220 mg/dL, and/or use of antilipemic therapy)
Liver disease or ALT serum concentrations greater than 1.5 times the upper laboratory
reference limit
Hyperbilirubinemia (serum total bilirubin greater than 1.5 mg/dL)
Renal insufficiency or estimated creatinine clearance less than or equal to 50 mL/min (MDRD
equation)
Anemia (Hemoglobin concentration less than or equal to 11.1 g/dL females, and 12.7 g/dL
males)
History of cholecystectomy or cholelithiasis (by ultrasound at screening).
History of malabsorption, or food allergies/intolerances that would preclude participant
from consuming foods required for study
Claustrophobia
History of illicit drug or alcohol abuse within the last 5 years; current use of illicit
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, energy expenditure or bile acid secretion
History of weight loss or weight gain of greater than 3 percent body weight over the past 2
months (self-reported)
Pregnancy/breastfeeding/hormonal contraceptive use and childbirth within the last 6 months
Perimenopausal (as self-described within two years from onset of amenorrhea or current
complaints of hot flashes)
Current smoker
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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