Effects of Diet Changes on Metabolism
Condition: Obesity
Study type: Observational

Summary: 
      This study, conducted at the NIH Clinical Research Unit at the Phoenix Indian Medical Center,
      will examine how the body s metabolism (energy expenditure) changes when people overeat and
      when they fast and how different diets (e.g., high-protein or high-fat) affect metabolism.
      The results may provide information about whether there are mechanisms that make some people
      more resistant than others to gaining weight when they eat more.

      Non-smoking healthy subjects between 18 and 55 years of age who weigh no more than 350 pounds
      may be eligible for this study. Participants undergo the following procedures:

        -  Pregnancy test for women of childbearing age.

        -  Oral glucose tolerance test. For this test, an I.V. line (needle attached to a plastic
           tube) is inserted into a vein to allow several blood draws without repeated needle
           sticks. After the first blood sample is drawn, the subject drinks a cola-flavored sugar
           solution. Five additional blood samples are then drawn over 3 hours.

        -  Blood test for DNA (genetic) studies related to obesity, diabetes and related medical
           problems.

        -  DEXA scan. This test measures body fat. The subject lies on a table while a very small
           dose of X-rays is passed through the body.

        -  Respiratory chamber. This test measures how many calories the body burns a day and
           assesses energy balance between intake and expenditure. Subjects stay in a room with two
           windows, equipped with a sink, toilet, television and DVD player, desk, chair, telephone
           and bed for 24 hours. The test is repeated five times during the first 18-day admission
           and 3 times during the second 13-day admission. For the first two sessions, subjects are
           fed a diet equal to the amount of energy their body uses. For the next 6 stays they are
           fed double the amount of calories their body usually uses for 5 of the stays and fast
           (consume nothing but water and soda without caffeine or calories) during 1 stay. The
           overfeeding diets may be high or low in protein, normal in protein, or high in fat.
           Blood tests are done on the day of each respiratory chamber session and a 24-hour urine
           sample is collected for one day while in the chamber.

        -  Eating behavior questionnaires.

        -  Psychological performance tests.

      Some participants are asked to volunteer to repeat two of the chamber studies to validate the
      measurements. The repeat session includes only the fasting and the overfeeding with normal
      protein content.

      All participants are followed at 6 months with blood tests, a DEXA scan, and urine tests
      (including pregnancy test for women). At annual visits for years 1 through 7, participants
      have the 6-month tests plus an oral glucose tolerance test.

      ...
    

Detailed description: 
      Some people appear to be more resistant than others to gaining weight when they overeat,
      though they do not increase their physical activity. This may indicate that adaptive
      mechanisms exist, which lead to wasting as heat part of the excess calories taken in. Such
      mechanisms exist in rodents including activation of brown fat, a tissue which can also
      convert calories to heat for warmth. Human studies have provided conflicting results. A pilot
      study on the relationship of the weight change over time with the changes in the amount of
      energy an individual uses over 24 hours (energy expenditure, EE) with 48-h overfeeding (OF)
      and fasting (F) in Pima Indian men has shown that persons with the greatest increase in EE
      with OF and the smallest decrease in EE with F gained the least weight over time, indicating
      that the ability to waste more calories when overfed may reduce weight gain. Other studies,
      however, have not shown this relationship. In addition, it has been proposed that unbalanced
      diets can help magnify these effects. The aims of this study are to test whether (a) the
      changes in EE in response to 24-h OF and F predict changes in weight over two years, and (b)
      high-carbohydrate diets or diets with high or low protein amounts may magnify the metabolic
      response to 24-h OF compared to normal protein and high-fat diets. 64 volunteers will be
      evaluated at baseline, 6 months and on a yearly basis for up to 7 years. At baseline,
      subjects will undergo 8 24-h sessions in a human respiratory chamber to measure EE while on a
      weight-maintaining diet, and then in random order: fasting, 200% OF on a normal-protein diet,
      200% OF on a high fat, low-protein diet, 200% OF on a high-fat, normal-protein diet, 200% OF
      on a high fat, high protein diet, and 200% OF on a high-carbohydrate, normal-protein diet.
      Fifteen volunteers will have two additional chambers to try and understand if the source of
      carbohydrates, i.e. simple sugars versus complex carbohydrates, in a high carbohydrate diet
      affect metabolism. Thirty volunteers are planned to also undergo 2 positron emission
      tomography (PET) studies to look at the relationship of brown fat with EE in adult humans.
      (As of April 2021, we will stop performing the PET scans; 24 volunteers have completed them
      and we have acquired sufficient data.) Body weight and composition will be measured at each
      subsequent admission. Hormonal measurements to find determinants of adaptive changes in EE in
      response to OF and F will also be performed. This study will provide significant insights
      into possible mechanisms that may help people resist weight gain and obesity.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Residents of the Phoenix metropolitan area
      
Keywords: Energy Expenditure; Adaptive Thermogenesis; Low-protein Overfeeding; Fasting; Weight Gain; Natural History