Metabolism and Thyroid Hormone Changes During Exposure to Cold Temperatures
Condition: Obesity
MeSH terms: Obesity; Thyroid Diseases
Study type: Interventional

Summary: 
      This study will examine how body metabolism adjusts to small changes in environmental
      temperature and how it may be related to weight loss.

      Healthy, non-obese individuals between 18 and 60 years of age may be eligible for this study.
      The study consists of one screening visit and one 5-day admission to the NIH Clinical Center
      for the following procedures:

      Diet: Participants follow a proscribed diet consisting of 50% carbohydrates, 20% protein and
      30% fat.

      DEXA scan to measure body fat. Subjects lie on a table above a source of X-rays while a very
      small dose of X-rays is passed through the body.

      Air displacement plethysmography (Bod-Pod) to study fat composition: Subjects sit in a small
      booth for 10 minutes wearing a swim suit and breathing normally through a tube. This test
      measures the person s weight and volume precisely.

      Metabolic room: Subjects stay 12 hours in a specialized room designed to measure the amount
      of oxygen breathed in and the amount of carbon dioxide breathed out. The room contains a
      private toilet and sink, treadmill, bed, desk, window, telephone and computer with television
      and internet access. While in this room, subjects undergo the following:

        -  Continuous heart rate monitor: Subjects wear an EKG monitor to analyze heart rate
           variability.

        -  Spontaneous movements: Subjects wear portable accelerometers at the hip and wrist to
           measure spontaneous physical movements.

        -  Continuous temperature monitor: Subjects swallow a small capsule that transmits internal
           body temperature via miniature, wireless sensors. Adhesive patches placed on the skin
           monitor external body temperature.

        -  Blood and urine collections: Subjects collect all of their urine during the 12 hours
           they are in the metabolic room. Blood samples are taken at specified intervals through a
           catheter that has been placed in a vein.

        -  Microdialysis: A small needle is placed into fat tissue just under the skin on the
           abdomen. A solution containing a minimal amount of ethanol is infused and samples of
           fluid are collected every 20 minutes as it leaves the fat pad. This helps determine the
           metabolism level. This procedure starts 30 minutes before entering the metabolic room
           and continues until the subject leaves the room.

      Fat tissue biopsy: A small piece of fat tissue is withdrawn through a needle from under the
      skin on the abdomen. The sample is used to study fat tissue size and ability to store sugar.
    

Detailed description: 
      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.
    

Intervention name(s): Exposure to Cold Temperature
Intervention type(s): Procedure
Allocation: Randomized
Intervention model: Crossover Assignment
Primary purpose: Other
Keywords: Thyroid; Thermoregulation; Catecholamines; Energy Expenditure; Obesity; Healthy Volunteer; HV