Regulation of Muscle Protein Phenotype in Humans With Obesity

NCT04700800 | Completed Results

• 2 other identifiers: 20-003294R01DK123441
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity

Outcome Measures

Primary Outcomes (3)

• Whole-Muscle Protein Synthesis

  Protein synthesis rates in whole muscle were quantified as the fractional synthesis rate (FSR), expressed as %/hour - representing the percentage of the entire muscle protein pool newly synthesized per hour. Protein synthesis rates were determined by continuous infusion of a stable isotope-labeled amino acid tracer, followed by measurement of tracer incorporation into the muscle proteins over time. Changes in FSR from baseline were evaluated in response to combined exercise and amino acid infusion.

  9 Hours

• Synthesis Rates of the Three Myosin Heavy Chain Isoforms (MHC I, MHC IIa, and MHC IIx)

  Synthesis rates of the myosin heavy chain protein isoforms were quantified as the fractional synthesis rate (FSR), expressed as %/hour - representing the percentage of each of the three myosin heavy chain isoform protein pool newly synthesized per hour. Protein synthesis rates were determined by continuous infusion of a stable isotope-labeled amino acid tracer, followed by measurement of tracer incorporation into each of the three myosin heavy chain isoform protein Changes in FSR from baseline were evaluated in response to combined exercise and amino acid infusion.

  9 Hours

• Messenger RNA (mRNA) Expression of Three Myosin Heavy Chain Isoforms (MHC I, MHC IIa, and MHC IIx)

  Messenger RNA (mRNA) expressions of the myosin heavy chain isoforms were determined by measuring the abundance of the three specific transcripts of the myosin heavy chain isoforms. mRNA was measured using quantitative reverse transcription PCR (qRT-PCR). Changes in mRNA expression from baseline were evaluated in response to combined exercise and amino acid infusion.

  9 Hours

Study Arms (2)

Subjects with obesity

EXPERIMENTAL

Exercise followed by infusion of amino acids

Other: Exercise

Lean Subjects

ACTIVE COMPARATOR

Exercise followed by infusion of amino acids

Other: Exercise

Interventions

Exercise OTHER

Exercise at 65% of heart rate reserve

Lean Subjects; Subjects with obesity

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

MeSH Terms

Conditions

Obesity

Interventions

Exercise

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Lori Roust
• Organization: Mayo Clinic

Roust.Lori@mayo.edu

(602) 543-4254

Study Officials

• Lori R Roust, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Christos S Katsanos, PhD

  Arizona State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 21, 2020
• First Posted: January 8, 2021
• Study Start: October 7, 2021
• Primary Completion: October 2, 2024
• Study Completion: October 2, 2024
• Last Updated: November 5, 2025
• Results First Posted: November 5, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)