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| ID | Type | Description | Link |
|---|---|---|---|
| R01DK123441 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Subjects with obesity | Experimental | Exercise followed by infusion of amino acids |
|
| Lean Subjects | Active Comparator | Exercise followed by infusion of amino acids |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Exercise | Other | Exercise at 65% of heart rate reserve |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lori R Roust, MD | Mayo Clinic | Principal Investigator |
| Christos S Katsanos, PhD | Arizona State University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic in Arizona | Scottsdale | Arizona | 85259 | United States |
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Of the participants that signed the consent form, 10 were screen failures, 11 withdrew, 4 declined participation, and 1 was enrolled but did not proceed. Twenty-three completed the entire study with one participant had data collected as did part of the study, for a total of 22 with data collected.
A total of 48 participants signed informed consent.
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| ID | Title | Description |
|---|---|---|
| FG000 | Participants with Obesity | Participants with Obesity performing acute aerobic exercise followed by infusion of amino acids, with measurements take before and after exercise+amino acid infusion |
| FG001 | Lean participants | Healthy lean participants performing acute aerobic exercise followed by infusion of amino acids, with measurements take before and after exercise+amino acid infusion |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Participants with Obesity | Participants with Obesity performing acute aerobic exercise followed by infusion of amino acids, with measurements take before and after exercise+amino acid infusion |
| BG001 | Lean paticipants |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | %/hr | 9 Hours |
|
Up to 6 months after enrollment in the study.
Levels of adverse events were defined as: Mild, Moderate, Severe (severe would correspond to serious)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Participants with Obesity | Participants with Obesity performing acute aerobic exercise followed by infusion of amino acids, with measurements take before and after exercise+amino acid infusion |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Numbness and soreness on the site of muscle biopsy few days after the procedure | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lori Roust | Mayo Clinic | (602) 543-4254 | Roust.Lori@mayo.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 23, 2024 | Aug 19, 2025 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 14, 2024 | May 1, 2025 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D015444 | Exercise |
| ID | Term |
|---|---|
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
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Healthy lean participants performing acute aerobic exercise followed by infusion of amino acids, with measurements take before and after exercise+amino acid infusion
| BG002 | Total | Total of all reporting groups |
| Standard Deviation |
| Years |
|
| Sex: Female, Male | Sex | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Hispanic/Non-Hispanic | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Lean participants |
Healthy lean participants performing acute aerobic exercise followed by infusion of amino acids, with measurements take before and after exercise+amino acid infusion |
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | %/hr | 9 Hours |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | Arbitrary Units | 9 Hours |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| 2 |
| 10 |
| EG001 | Lean participants | Healthy lean participants performing acute aerobic exercise followed by infusion of amino acids, with measurements take before and after exercise+amino acid infusion | 0 | 12 | 0 | 12 | 6 | 12 |
|
| Nauseous and/or lightheaded | Nervous system disorders | Non-systematic Assessment |
|
| Numbness in mouth | Gastrointestinal disorders | Non-systematic Assessment |
|
| Unable to drink the drink provided for the oral glucose tolerance test | Gastrointestinal disorders | Non-systematic Assessment |
|
| Car accident outside the study procedures, preventing further participation in the study | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |