Obesity
Conditions
Brief 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.
Interventions
BEHAVIORALLow carbohydrate diet
Composition (by proportion of calories) : 15% carbohydrate, 65% fat, 20% protein
BEHAVIORALModerate carbohydrate diet
Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein
BEHAVIORALHigh carbohydrate diet
Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein
Sponsors
Framingham State University
Brigham and Women's Hospital
Boston Medical Center
Nutrition Science Initiative
New Balance Foundation
Boston Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion Criteria (as detailed in Framingham State Food Study, NCT02068885) * Aged 18 to 65 years * BMI ≥ 25 kg/m2 * BMI \< 40 kg/m2 and weight ≤ 300 lbs (136 kg) * Medical clearance from a primary care provider * Student or employee at Framingham State University throughout enrollment in the study * Willing and able to eat and drink only the foods and beverages on the study menus * Willing to eat in the dining hall * Willing to abstain from consuming alcohol during participation Additional Inclusion Criteria: • Willing to undergo additional procedures in this ancillary study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Late postprandial energy availability | 10 - 15 weeks after initiation of test diets | Post-prandial energy availability calculated as the sum, in kcal/L, of energy from circulating metabolic fuels (glucose, non-esterified fatty acids, lactate and ketoacids), as measured during a 24 hr inpatient admission. Time of interest includes 2.5 - 5 hr in the postprandial period after breakfast, lunch and dinner. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lactate | 10 - 15 weeks after initiation of test diets | Concentration during 24-hr inpatient admission |
| Fasting energy availability | 10 - 15 weeks after initiation of test diet | Fasting energy availability calculated as the sum, in kcal/L, of energy from circulating metabolic fuels (glucose, non-esterified fatty acids, lactate and ketoacids), as measured during a 24 hr inpatient admission. |
| Total energy availability | 10 - 15 weeks after initiation of test diets | Total energy availability calculated as the sum, in kcal/L, of energy from circulating metabolic fuels (glucose, non-esterified fatty acids, lactate and ketoacids), as measured during a 24 hr inpatient admission. |
| Late postprandial energy availability, with lactate excluded | 10 - 15 weeks after initiation of test diets | Post-prandial energy availability calculated as the sum, in kcal/L, of energy from circulating metabolic fuels (glucose, non-esterified fatty acids, and ketoacids), as measured during a 24 hr inpatient admission. Time of interest includes 2.5 - 5 hr in the postprandial period after breakfast, lunch and dinner. (Lactate is metabolized primarily by the liver, which uses this substrate to produce glucose. Thus, including lactate in the calculation of metabolic fuels may comprise double counting -- and not accurately reflect actual fuel availability to body tissues) |
| Hunger | 10 - 15 weeks after initiation of test diets | Measured during a 24 hr inpatient admission. |
| Satiety | 10 - 15 weeks after initiation of test diets | Measured during a 24 hr inpatient admission. |
| Glucose | 10 - 15 weeks after initiation of test diets | Concentration during 24-hr inpatient admission |
| Non-esterified fatty acids | 10 - 15 weeks after initiation after test diet | Concentration during 24-hr inpatient admission |
| Ketoacids | 10 - 15 weeks after initiation of test diets | Concentration during 24-hr inpatient admission |
| Insulin | 10 - 15 weeks after initiation of test diets | Concentration during 24-hr inpatient admission |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adipose tissue histology | 10 - 15 weeks after initiation of test diets | Change from baseline. |
| Effect modification by insulin secretion | 10 - 15 weeks after initiation of test diets | We will test for an interaction by insulin secretion (as measured by plasma insulin 30 minutes into a standard oral glucose tolerance test) of the relationship between diet and metabolic fuels concentration. |
| Adipocyte studies of anabolic status | 10 - 15 weeks after initiation of test diets | Adipose tissue gene expression studies (assessed by mRNA levels of selected candidate genes involved in lipid storage, fatty acid and lipid biosynthesis, angiogenesis, inflammation). Change from baseline. |
Countries
United States
Outcome results
None listed