Metabolism and Thyroid Hormone Changes During Exposure to Cold Temperatures

Thyroid hormones play an important role in the modulation of energy metabolism by regulating the rate of thermogenesis, i.e. the amount of heat produced to maintain the stable core temperature of the organism. Clinically, hypo- and hyperthyroidism are associated with major changes of thermoregulation and energy expenditure. While in rodents the ability of thyroid hormones in regulating the temperature and energy expenditure in response to changes of temperature is well known, its actual role in humans is poorly understood. We hypothesize that humans will respond to exposure to moderate cold by increasing the energy expenditure mediated by the thyroid hormones action and, at the same time, by decreasing the heat dispersion. This randomized, cross-over study is aimed to analyze the changes in the thyroid hormones, energy expenditure and stress hormones in response to exposure to mild changes in environmental temperature. A total of 230 lean and overweight volunteers who are 18 years of age or older, following a two-day period of standardized diet, will be randomized to either a normal (75 (Infinite)F/24 (Infinite)C) or low-temperature (64 (Infinite)F/18 (Infinite)C) 12- or 24-hour stay in a temperature-controlled metabolic chamber. A standard meal will be provided after six hours of recording in studies performed during the daytime. After a two-day resting period the test will be then repeated at the second temperature. In order to visualize and quantify the metabolic activity of brown adipose tissue (BAT), twenty five lean study volunteers younger than 60 will be asked to undergo a 18-fluoro-deoxy-glucose PET-scan after each of the two 12-hour overnight stays in the metabolic chamber. In order to determine the impact of mitochondrial function on cold-stimulated BAT activity, a sub-group of volunteers who carry a mutation in the mitochondrial genes, succinate dehydrogenases, and age- and gender-matched control subjects, will undergo PET/CT scanning at the end of a 24-hour stay in the metabolic chamber at 18 (Infinite)C and 24 (Infinite)C. The following parameters will be recorded and analyzed: Changes in skin and core temperature, heart rate and its variability, energy expenditure, changes in circulating thyroid hormones, ACTH, cortisol, and catecholamines. Changes in glucose uptake in relation to changes in energy expenditure will be measured by PET-scan. The adipose tissue metabolism will be analyzed by microdialysis and study volunteers will be asked to undergo subcutaneous adipose tissue needle biopsy. The data gathered from this study will provide a comprehensive insight into the mechanism(s) regulating the energy metabolism in response to mild cold. The results obtained from the proposed experiments might lead to the characterization of a population of subjects who are requiring excessive energy expenditure to prevent hypothermia upon cold exposure. Thus, we hypothesize that in a subset of subjects an exposure to mild cold will produce a negative energy balance ultimately facilitating weight loss.