Protective Effect of Exercise on Acute High-fat Overfeeding (HFDEXC)

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.

Study Overview

• Status: Completed
• Conditions: Insulin Sensitivity/Resistance
• Intervention / Treatment: Behavioral: High Fat Overfeeding; Behavioral: High Fat Overfeeding + Exercise

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20052
      • Milken Institute School of Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Males or females between the ages of 20 and 40 years
• A body mass index (BMI) of 20.0 - 29.9 kg/m2.
• Low risk for risk of injury or health complications as determined by physical activity readiness questionnaire (PARQ).

Exclusion Criteria:

• Are currently taking any antioxidant supplementation (daily multivitamin not included), prescribed non-steroidal anti-inflammatory drugs (NSAIDS), antibiotics, steroids, or probiotics.
• Are currently taking any medications for management of cholesterol, diabetes, or body weight/obesity, or are undergoing hormone therapy.
• Are unwilling or unable to comply with study procedures, at the discretion of the investigators.
• Are unwilling to have biospecimens (blood and urine) collected and stored (only blood) for future research.
• Pregnant women - A urine pregnancy test will be conducted prior to any testing procedures.
• A history of disordered eating, including anorexia nervosa, bulimia nervosa, binge eating disorder, or avoidant restrictive food intake disorder or deemed high-risk for disordered eating via questionnaire.
• A history of gastrointestinal diseases, such as galactosemia, gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), Celiac disease, Crohn's disease, or lactose intolerance.
• Individuals with known allergies to wheat or gluten, milk, soy, tree nuts (e.g., almonds, walnuts, pecans), or peanuts.
• Deemed high risk for food insecurity via the Hunger Vital Sign screener.
• Have followed a ketogenic diet within the last three months or have been told to avoid a high-fat diet by a medical provider for risk of cardiovascular disease.
• Cardiorespiratory fitness (VO2max) below the 30th percentile for age and sex (measured at initial screening visit)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Fat Overfeeding; 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.	Behavioral: High Fat Overfeeding; Caloric intake 180% of daily caloric need with 65% from fat
Experimental: High Fat Overfeeding + Exercise; 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	Behavioral: High Fat Overfeeding + Exercise; Caloric intake 180% of daily caloric need with 65% from fat with acute moderate exercise (energy expenditure ~25% of daily caloric need).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Sensitivity via Oral Glucose Insulin Sensitivity Index	Oral Glucose Insulin Sensitivity	Immediately following high fat diet intervention

Secondary Outcome Measures

Outcome Measure	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	Carotid Femoral Pulse Wave Velcoity	Immediately following high fat diet intervention

Collaborators and Investigators

• Sponsor: George Washington University
• Investigators: Principal Investigator: Matthew Barberio, George Washington University

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2025
• Primary Completion (Actual): April 7, 2026
• Study Completion (Actual): April 9, 2026

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 8, 2026

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Exercise; Metabolism; Substrate Oxidation; Overfeeding; High Fat Diet
• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Hyperinsulinism; Behavior; Nutritional and Metabolic Diseases; Insulin Resistance; Motor Activity; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: NCR246197

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual data will be annonymized by study ID number and removed of any identifying information. Data will be shared upon reasonable request.
• IPD Sharing Time Frame: Upon publication, data will be shared upon reasonable request to the corresponding author.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No