Protective Effect of Exercise on Acute High-fat Overfeeding

NCT07633704 | Completed

• 1 other identifier: NCR246197
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Insulin Sensitivity/Resistance

Keywords

Metabolism; Exercise; Substrate Oxidation; Overfeeding; High Fat Diet

Outcome Measures

Primary Outcomes (1)

• Insulin Sensitivity via Oral Glucose Insulin Sensitivity Index

  Oral Glucose Insulin Sensitivity

  Immediately following high fat diet intervention

Secondary Outcomes (2)

• Metabolic Flexibility (Respiratory Exchange Ratio) via Indirect Calorimetry

  Immediately following high fat diet intervention

• Carotid Femoral Pulse Wave velocity

  Immediately following high fat diet intervention

Study Arms (2)

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.

Behavioral: High Fat Overfeeding

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

Behavioral: High Fat Overfeeding + Exercise

Interventions

High Fat Overfeeding BEHAVIORAL

Caloric intake 180% of daily caloric need with 65% from fat

High Fat Overfeeding

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).

High Fat Overfeeding + Exercise

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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)

Sponsors & Collaborators

• George Washington University: lead

Study Sites (1)

Milken Institute School of Public Health

Washington D.C., District of Columbia, 20052, United States

Location

MeSH Terms

Conditions

Insulin Resistance; Motor Activity

Interventions

Exercise

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Matthew Barberio

  George Washington University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 11, 2026
• First Posted: June 8, 2026
• Study Start: February 10, 2025
• Primary Completion: April 7, 2026
• Study Completion: April 9, 2026
• Last Updated: June 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: Upon publication, data will be shared upon reasonable request to the corresponding author.

Locations

US (1)