Thyroid Hormones Homeostasis and Energy Metabolism Changes During Stimulation of Endogenously Secreted Bile Acids (BAs)
Status:
Completed
Trial end date:
2012-08-21
Target enrollment:
Participant gender:
Summary
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 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.
Phase:
Phase 3
Details
Lead Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Treatments:
Bile Acids and Salts Hormones Ursodeoxycholic Acid