Muscle Protein Metabolism in Obesity

Study Overview
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Brief Summary
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Obesity is associated with reduced adenosine triphosphate (ATP) turnover in skeletal muscle, a condition that can impair muscle metabolism. The proposed research will discover mechanisms responsible for decreased content in mitochondrial proteins as well as in protein β-F1-ATPase, which is directly responsible for ATP assembly, in the muscle of obese individuals. This research will further examine the effectiveness of interventions, such as increased plasma amino acid availability and exercise, to increase the rate of production of mitochondrial proteins as well as that of β-F1-ATPase in the muscle of obese individuals. The findings will help to develop appropriate interventions to improve muscle ATP turnover and metabolism in obese people.

Official Title
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Regulation of Muscle ATP Synthase Beta Subunit Metabolism in Obesity

Conditions
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Obesity

Intervention / Treatment
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* Other: Increase in the levels of plasma amino acids
* Other: Aerobic exercise


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Body mass index (BMI): lean, 19-26 kg/m2; obese, 30-40 kg/m2 Availability of transportation Ability to sign informed consent form Exclusion criteria: Medication or supplements (i.e. amino acids, protein) known to affect protein metabolism Presence of acute illness History of liver disease Uncontrolled metabolic disease ECG documented abnormalities, atrial fibrillation, history of syncope, limiting or unstable angina, or congestive heart failure Chronically elevated blood pressure (systolic, >140 mmHg; diastolic, >100 mmHg) Cardiac pacemaker or other medical device implanted in the body Low hemoglobin or hematocrit Current participation in a weight-loss regimen, including extreme dietary practices Smoking Use of anabolic steroids or corticosteroids (within 3 months)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amino Acid Infusion in Lean<br>Amino Acid Infusion in Lean | Other: Increase in the levels of plasma amino acids<br>* Aminosyn 15%; 160 mg/kg FFM/h for 4 hours<br>|
| Experimental: Amino acid Infusion in Obese<br>Amino acid Infusion in Obese | Other: Increase in the levels of plasma amino acids<br>* Aminosyn 15%; 160 mg/kg FFM/h for 4 hours<br>|
| Experimental: Exercise in lean<br>Exercise in lean | Other: Aerobic exercise<br>* Moderate intensity for 45 minutes<br>|
| Experimental: Exercise in Obese<br>Exercise in Obese | Other: Aerobic exercise<br>* Moderate intensity for 45 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of synthesis of muscle proteins (mixed muscle proteins, mitochondrial proteins, β-F1-ATPase) |  | Measured during a 9-hour infusion study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| β-F1-ATPase mRNA expression; PGC-1 expression |  | Measured during a 9-hour infusion study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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muscle, mitochondria, amino acids, exercise