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NCT Number: NCT04700800

Regulation of Muscle Protein Phenotype in Humans With Obesity

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.

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Key information

Conditions

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

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Exercise

Other

Exercise at 65% of heart rate reserve

Primary outcomes

  1. Whole-Muscle Protein Synthesis

    Time frame: 9 Hours

    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.

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

    Time frame: 9 Hours

    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.

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

    Time frame: 9 Hours

    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.

Sponsors and collaborators

Lead sponsor

Mayo Clinic

Other

Collaborators

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

Registry information

Important dates

Study start
2021
Primary completion
2024
Study completion
2024
First posted
Jan 8, 2021
Registry last updated
Nov 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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