Metabolic Adaptations to Weight Loss With and Without Exercise

NCT05806801 | Recruiting

• 1 other identifier: HUM00220220
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

Study Purpose: The combination of caloric restriction and exercise is the most common first-line treatment for obesity-related disorders, yet we know very little about how these two very different treatments work together. A deeper understanding about mechanisms underlying the health benefits of adding exercise to a weight loss program will not only aid efforts to optimize more effective lifestyle interventions, but it can also uncover novel targets for the treatment/prevention of obesity-related diseases. Although a reduction in body fat is the fundamental adaptation to weight loss, we know almost nothing about the effects that adding exercise has on structural and functional changes within fat tissue that may further enhance metabolic health. This is very important because many obesity-related metabolic health complications are tightly linked with abnormalities in abdominal fat tissue. We argue exercise-induced modifications in abdominal fat tissue will reveal persistent health benefits even if some weight is regained Study Summary: 10% Weight Loss Phase - Subject participation in the study will involve a series of metabolic tests before, at midpoint, and after undergoing a 10% weight loss program (with or without exercise training depending on group randomization). During this, subjects will be randomized into one of two different experimental groups:

1. 1.Moderate Intensity Continuous Training (MICT) exercise group
2. 2.No exercise (control) group

Conditions

Obesity; Metabolic Disease; Insulin Sensitivity; Insulin Resistance; Weight Loss; Metabolic Syndrome

Outcome Measures

Primary Outcomes (4)

• Insulin sensitivity

  a hyperinsulinemic-euglycemic clamp will be used to quantify peripheral insulin sensitivity

  2 hours

• Fatty acid turnover

  stable isotope tracer infusion methods will be used to assess fatty acid turnover

  2 hours

• Adipose tissue capillarization

  measured immunohistochemically using an antibody for CD31, quantified using ImageJ software

  30 minutes

• Adipose tissue fibrosis

  measured histologically using Sirus Red Staining, quantified using ImageJ software

  30 minutes

Secondary Outcomes (3)

• Body weight change

  6 months

• Body fat mass

  30 minutes

• Oral Glucose Tolerance Test (OGTT)

  2 hours

Study Arms (2)

Moderate Intensity Continuous Training (MICT) exercise group

EXPERIMENTAL

45 minutes of continuous steady-state exercise at 70% maximal heart rate throughout the 10% weight loss phase of the study

Behavioral: MICT Exercise

No exercise (Control)

EXPERIMENTAL

to remain sedentary (no planned physical exercise) throughout the duration of the 10% weight loss phase of the study

Behavioral: No Exercise (Control)

Interventions

MICT Exercise BEHAVIORAL

Subjects randomized into this group will complete a moderate intensity continuous exercise 4 days/week.

Moderate Intensity Continuous Training (MICT) exercise group

No Exercise (Control) BEHAVIORAL

Subjects randomized into this group will remain sedentary throughout the duration of the study.

No exercise (Control)

Eligibility Criteria

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

You may qualify if:

• Age: 18-40
• Body Mass Index: 30-40 kg/m2
• Weight stable (±3kg for greater than or equal to about 2 months)
• No regularly planned exercise/physical activity
• Women must have regularly occurring menses and must be premenopausal

You may not qualify if:

• EKG abnormalities
• Evidence/history of cardiovascular disease, diabetes or other metabolic disease
• Medications known to affect lipid or glucose metabolism
• Pregnant or lactating
• Tobacco or e-cigarette use
• Prior experience of hypersensitivity to insulin, human albumin, and potassium chloride injection.
• Allergies/hypersensitivity to local anesthetics of the amide type (e.g., lidocaine)
• History of hyperkalemia or potential for developing hyperkalemia (including but not limited to taking drugs that may induce hyperkalemia such as cardiac glycosides or potassium sparing diuretics)

Sponsors & Collaborators

• University of Michigan: lead

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

MeSH Terms

Conditions

Obesity; Metabolic Diseases; Metabolic Syndrome; Insulin Resistance; Weight Loss

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Body Weight Changes

Study Officials

• Jeffrey Horowitz, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Suzette M Howton

CONTACT

734-647-9850; suzetter@med.umich.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Movement Science and Director of the Substrate Metabolism Laboratory (SML) at the University of Michigan School of Kinesiology

Study Record Dates

• First Submitted: March 28, 2023
• First Posted: April 10, 2023
• Study Start: July 19, 2023
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): May 31, 2028
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

US (1)