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Metabolic flexibility is the ability to switch rapidly from one substrate (i.e. fuel source) to another (e.g. fats to carbohydrates) in response to ingested foods. Worse metabolic flexibility is linked to worse metabolic outcomes, but exercise is thought to be protective against nutrient excess. We will conduct a standard oral glucose tolerance test (OGTT) to assess insulin resistance and metabolic flexibility. Participants will be randomized to a 24-hour hypercaloric, high-fat diet (HFD) with and without an exercise bout. During the hypercaloric HFD, participants will eat extra calories with more calories from fat than normal, which is expected to increase insulin resistance. After each arm of the high-fat diet, we will repeat the OGTT. During each OGTT, expired gases will be analyzed noninvasively to determine metablic flexibility. Insulin resistance will be determined with blood drawn during each OGTT. By comparing metabolic flexiblity and insulin resistance before and after the normal diet and after the high-fat diet intervention, a better understanding of how insulin resistance affects metabolism and how exercise can be protective will be developed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High Fat Overfeeding | Experimental | Resting metabolic rate will be used estimate total caloric need. We will use this estimate to create a daily target calorie intake and target fat intake for the High-Fat Diets (HFD) in the study. During the high-fat diet, subjects will eat 80% more calories than necessary with at least 65% of the calories coming from fat for one day. |
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| High Fat Overfeeding + Exercise | Experimental | On the day of High Fat Overfeeding (See High Fat Overfeeding arm description), subjects will complete a single bout of exercise. The duration of exercise will be individualized to ~25% of daily energy needs.The intensity of exercise will be individualized to be at a low intensity in the moderate domain. Extra foods will be provided to match energy balance across the high-fat overfeeding days |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| High Fat Overfeeding | Behavioral | Caloric intake 180% of daily caloric need with 65% from fat |
|
| Measure | Description | Time Frame |
|---|---|---|
| Insulin Sensitivity via Oral Glucose Insulin Sensitivity Index | Oral Glucose Insulin Sensitivity | Immediately following high fat diet intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Metabolic Flexibility (Respiratory Exchange Ratio) via Indirect Calorimetry | Respiratory Exchange Ratio, Glucose Oxidation, Fatty Acid Oxidation | Immediately following high fat diet intervention |
| Carotid Femoral Pulse Wave velocity |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Matthew Barberio | George Washington University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Milken Institute School of Public Health | Washington D.C. | District of Columbia | 20052 | United States |
Individual data will be annonymized by study ID number and removed of any identifying information. Data will be shared upon reasonable request.
Upon publication, data will be shared upon reasonable request to the corresponding author.
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| D009043 | Motor Activity |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D015444 | Exercise |
| ID | Term |
|---|---|
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
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| High Fat Overfeeding + Exercise | Behavioral | Caloric intake 180% of daily caloric need with 65% from fat with acute moderate exercise (energy expenditure ~25% of daily caloric need). |
|
Carotid Femoral Pulse Wave Velcoity
| Immediately following high fat diet intervention |
| D001519 | Behavior |