Regulation of Muscle Protein Phenotype in Humans With Obesity

NCT ID: NCT04700800

Last Updated: 2025-11-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-07
• Study Completion Date: 2024-10-02

Brief Summary

A hallmark of muscle changes in obesity is an altered muscle fiber type profile, characterized by a reduced proportion of Type I fibers - a shift associated with adverse obesity-related health outcomes. This alteration can be linked to changes in the expression of myosin heavy chain (MHC) protein isoforms in the skeletal muscle of individuals with obesity. The investigators aim to modulate the metabolism of muscle MHC isoforms to uncover the biological mechanisms underlying this disrupted expression pattern in muscle of humans with obesity.

Detailed Description

Humans with obesity have typically lower proportion of Type I muscle fibers in skeletal muscle. These fiber types, known for their high capacity for glucose uptake, have also greater sensitivity to fuel metabolism compared with Type II fibers, even within the adverse metabolic environment of obesity. Altered expression of skeletal muscle myosin heavy chain (MHC) protein isoforms, molecular marker of fiber types, may explain this shift.

This project aims to uncover the biological mechanisms sustaining disrupted MHC protein metabolism in the skeletal muscle of individuals with obesity. The investigators will compare overall protein metabolism between humans with obesity and lean controls, with a specific focus on MHC isoforms. They will assess MHC isoform gene expression, associated molecular regulators, and synthesis rates of the MHC isoforms involved in muscle fiber programming. Acute aerobic exercise and elevated plasma amino acids will be used as experimental tools to target transcriptional and translational processes related to MHC gene expression. The findings are expected to reveal mechanisms responsible for the unfavorable fiber type profile observed in the skeletal muscle of humans with obesity.

Conditions

Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Subjects with obesity

Exercise followed by infusion of amino acids

Group Type: EXPERIMENTAL

Exercise

Intervention Type: OTHER

Exercise at 65% of heart rate reserve

Lean Subjects

Exercise followed by infusion of amino acids

Group Type: ACTIVE_COMPARATOR

Exercise

Intervention Type: OTHER

Exercise at 65% of heart rate reserve

Interventions

Exercise

Exercise at 65% of heart rate reserve

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• ability to sign informed consent form
• body mass index (BMI), 18-26 kg/m2 (lean subjects), 32-50 kg/m2 (subjects with obesity)

Exclusion Criteria

• prescription or over-the-counter medication
• supplements known to affect protein metabolism (i.e., amino acids, protein, omega-3 fatty acids)
• diabetes
• acute illness
• liver disease
• uncontrolled metabolic disease, including renal disease
• heart disease related to atrial fibrillation, history of syncope, limiting or unstable angina, congestive heart failure or ECG documented abnormalities
• low hemoglobin or hematocrit
• use of anabolic steroids or corticosteroids (within 3 months)
• not classified as inactive/sedentary based on the Stanford Brief Activity Survey and accelerometry data
• participation in a weight-loss regimen
• extreme dietary practices (i.e., vegan, vegetarian)
• smoking
• pregnancy
• gastro-intestinal surgery
• any other condition or event considered exclusionary by the PI and the study physician.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Lori R. Roust

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lori R Roust, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Christos S Katsanos, PhD

Role: PRINCIPAL_INVESTIGATOR

Arizona State University

Locations

Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R01DK123441

Identifier Type: NIH

Identifier Source: secondary_id

View Link

20-003294

Identifier Type: -

Identifier Source: org_study_id