Metabolic Fuels Study
Condition: Obesity
Study type: Interventional

Summary: 
      This study will evaluate a potential physiologic mechanism underlying the effects of dietary
      composition on control of body weight
    

Detailed description: 
      The challenge in maintaining long-term weight loss is well known, however new research
      suggests diet quality may be the driving factor. A pilot study from our group demonstrated
      that a higher carbohydrate-containing diet was associated with lower total energy expenditure
      during weight loss maintenance (Ebbeling et al). These findings will be confirmed in the
      ongoing Framingham State Food Study (NCT02068885): Following weight loss on a standard diet,
      150 overweight or obese adults (aged 18 to 65 years) will be randomized to one of three
      weight-loss maintenance diets varying in carbohydrate to fat ratios for 20 weeks.

      However, the specific mechanisms underlying the calorie-independent effects of diet remain
      unclear. Another study from our group demonstrated lower energy availability (calculated
      based on caloric content of circulating metabolic fuel concentrations) in the fasting and
      late post-prandial periods in 8 overweight or obese young adults who were maintained on a
      low-fat (high-carbohydrate) diet (Walsh et al). We hypothesize that this lower metabolic fuel
      availability on a high carbohydrate diet results in part from increased anabolic changes
      within the adipocyte, favoring fat storage in preference to oxidation.

      We will invite subjects already enrolled in the Framingham State Food Study to participate,
      aiming for a total of 30 subjects (with the goal of approximately equal numbers per diet
      group following randomization to assigned test diet in the parent study). Participants will
      be admitted to a research unit for a 24-hour period during weight maintenance on the test
      diet, during which they will undergo frequent blood sampling for the measurement of
      circulating metabolic fuels, hunger and satiety ratings, while consuming their assigned diet
      meals. Each participant will also undergo two abdominal subcutaneous fat aspiration biopsies
      under local anesthesia, the first immediately following weight loss (before initiating the
      test diet) and the second during weight maintenance, in order to perform gene expression
      analyses on the adipose tissue. Our main outcomes will be a comparison in energy availability
      (the sum of energy in the major metabolic fuels in the blood) between diet groups in the late
      postprandial period and changes in adipose tissue gene expression within-individuals and by
      diet group assignment. Other outcomes will include differences in hunger and satiety ratings,
      total 24-hour energy availability, and specific metabolic fuel concentrations.
    

Intervention name(s): Low carbohydrate diet; Moderate carbohydrate diet; High carbohydrate diet
Intervention type(s): Behavioral; Behavioral; Behavioral
Intervention description(s): Composition (by proportion of calories) : 15% carbohydrate, 65% fat, 20% protein; Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein; Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein
Other intervention name(s): Composition : 15% carbohydrate, 65% fat, 20% protein
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Basic Science