Chronic Cold Exposure and Energy Metabolism in Humans
Condition: Healthy
Study type: Observational

Summary: 
      Background:

      - Researchers are studying how metabolism and hormone levels change in response to mild
      changes in environmental temperature. Changes in metabolism may lessen with time because of
      hormonal adaptations. If this increase in metabolism continues for a longer period, mild cold
      exposure may cause weight loss. It is unclear whether exposure to a warmer temperature may
      cause opposite changes in metabolism. Researchers want to see if longer exposure (1 month) to
      different temperatures can affect how the body uses energy.

      Objectives:

      - To test changes in energy metabolism in response to different room temperatures.

      Eligibility:

      - Healthy men between 18 and 40 years of age.

      Design:

        -  The entire study will last for 4 months. It will involve a screening visit and a 4-month
           inpatient stay at the National Institutes of Health Clinical Center. The inpatient stay
           will be in a private room at the Metabolic Clinical Research unit. Study participants
           will be required to stay in the Metabolic Clinical Research unit during the night, but
           are free to leave during the day.

        -  At the screening visit, participants will have a physical exam and medical history.
           Blood samples will be collected. A heart function test and diet questionnaire will also
           be given.

        -  During the first month, the temperature of the private room will be set at to 75.2
           degrees F. This will allow the body to become used to the testing environment.

        -  During the second month, the temperature will be set to either a cool (66.2 degrees F)
           or a warm (80.6 degrees F) temperature.

        -  During the third month, the temperature will return to 75.2 degrees F.

        -  During the fourth month, the temperature will be altered to the opposite temperature to
           the one set in the second month.

        -  Throughout stay, participants will have daily temperature monitoring and will keep a
           food diary. Once a week, they will collect all of their urine for 24 hours. Once a
           month, they will spend 24 hours in a metabolic suite to study their metabolism rate.

        -  Throughout stay, the food will be provided as part of the study.

        -  During the first and third month (75.2 degrees F) the participants will be allowed to
           leave the Metabolic Clinical Research unit during the weekends, while during the second
           and forth month (66.2 or 80.6 degrees F), the participants will be allowed to spend one
           weekend out of the Metabolic Clinical Research unit.

        -  Other tests, such as body scans, fat tissue samples, and imaging studies, will be
           performed as needed.
    

Detailed description: 
      Obesity is a major health issue worldwide. Despite global research efforts, effective
      treatments for obesity are limited. There are two kinds of fat in the body: white fat and
      brown fat. White fat functions mainly as an energy-storing organ and in excess results in
      obesity and complications such as diabetes and high blood pressure. Brown fat on the other
      hand releases the energy stored in fat as heat. It protects small animals and newborn human
      infants from cold temperatures.

      Recent advances in imaging techniques have revealed brown fat to be present in significant
      amount in adult humans. Using PET scanning, brown fat is shown to be more abundant in lean
      and younger individuals, suggesting that brown fat may regulate energy balance and
      metabolism. In a previous study we showed that following exposure to mild cold (19degree
      C/66degree F), the activity of brown fat was increased by nearly 10% and the energy
      expenditure by over 6%. Over time, these changes might result in substantial weight loss.
      However this has not been investigated and it is uncertain whether long-term cold exposure
      can sustain the increased activity of brown fat. In order to determine the therapeutic
      potential of brown fat activation, we designed a study investigating the effects of cold
      exposure over a long period.

      We hypothesize that adult humans can be cold-acclimatized through mild cold exposure over a
      month. Brown fat activity can be increased and sustained by cold stimulation, which could
      result in beneficial metabolic changes in the body.

      The aims of the current project are to:

        1. determine whether brown fat can be stimulated by exposure to mild cold

        2. investigate the metabolic consequences of long-term cold exposure

      Volunteers will be randomly assigned to sleep overnight in the Metabolic Clinical Research
      Unit at NIH, set at either mild cold (19degree C/66degree F) or mild warm (27degree
      C/81degree F), with a lead-in period and a wash-out period before crossing over, during which
      the temperature will be ambient (24degree C/75 degree F). Volunteers can conduct their
      regular activities during the day. Each period will be 1 month in duration. At the end of
      each month, volunteers will be evaluated for their metabolic response to a mild cold
      challenge for 24 hours (19degree C/66degree F) to determine whether brown fat function and
      activity have been altered by temperature acclimatization in the previous month.

      Significance: Based on its role in energy homeostasis and protection against obesity in
      animals, brown fat is likely to have a similar role in adult humans. Determining the
      contribution of brown fat-mediated cold acclimatization to long term energy balance may lead
      to novel treatment strategies of obesity.
    

Observational model: Cohort
Time perspective: Prospective
Keywords: Adaptive Thermogenesis; Adipose Tissue; Body Composition; Body Weight Regulation; Brown Adipose Tissue