Exercise Response in Humans With Obesity

Study Overview
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Brief Summary
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This study is being done to understand how chronic inflammation affects muscle function and responses to exercise.

Official Title
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Exercise Response in Humans With Obesity

Conditions
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Obese

Intervention / Treatment
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* Diagnostic Test: Treadmill Test
* Diagnostic Test: Strength Test
* Diagnostic Test: Dual-Energy X-Ray Absorptiometry
* Procedure: Muscle Biopsy
* Procedure: Fat Biopsy
* Diagnostic Test: Resting Energy Expenditure
* Diagnostic Test: Magnetic resonance imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Obese men and women ≥ 20 and ≤ 45 years of age. Exclusion Criteria: Diabetes or fasting plasma glucose >126 mg/dL Anemia (female subjects hemoglobin of <11 g/dl and male subjects hemoglobin <12 g/dl) Active coronary artery disease or history of unstable macrovascular disease (unstable angina, myocardial infarction, stroke, and revascularization of coronary, peripheral or carotid artery within 3 months of recruitment) Renal failure (serum creatinine > 1.5mg/dl) Chronic active liver disease defined as aspartate aminotransferase (AST)>144 IU/L or alanine transaminase (ALT) >165 IU/L) Oral warfarin group medications or history of blood clotting disorders. Smoking Pregnancy or breastfeeding Alcohol consumption greater than 2 glasses/day or other substance abuse Untreated or uncontrolled hypothyroidism Debilitating chronic disease (at the discretion of the investigators)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lean Group<br>Participants with body mass index 20-25 kg/m^2 will complete an outpatient study visit (body composition, blood draw, treadmill test, strength test) and an inpatient visit (muscle biopsies, fat biopsies, indirect calorimetry, exercise test). | Diagnostic Test: Treadmill Test<br>* Measurement of whole-body fitness level. Walking or running on a treadmill and breathing into a machine that measures oxygen level during test. Heart rhythm is continuously monitored during exercise using an electrocardiogram (ECG).<br>Diagnostic Test: Strength Test<br>* Measure the strength of leg muscles by kicking against a machine with resistance.<br>Diagnostic Test: Dual-Energy X-Ray Absorptiometry<br>* Body composition measurement.<br>* Other names: DEXA;Procedure: Muscle Biopsy<br>* Obtain a small piece of muscles from the upper part of the legs<br>Procedure: Fat Biopsy<br>* Fat sample taken from abdomen<br>Diagnostic Test: Resting Energy Expenditure<br>* Measured by indirect calorimetry. Measures how much energy the body uses at rest by placing a special plastic dome over the head while resting quietly for 30 minutes. Measures oxygen breathed in and carbon dioxide breathed out.<br>* Other names: REE;Diagnostic Test: Magnetic resonance imaging<br>* MRI on upper leg to look at fat and muscle<br>* Other names: MRI;|
| Obese Group<br>Participants with body mass index 30-45 kg/m^2 will complete an outpatient study visit (body composition, blood draw, treadmill test, strength test) and an inpatient visit (muscle biopsies, fat biopsies, indirect calorimetry, exercise test). | Diagnostic Test: Treadmill Test<br>* Measurement of whole-body fitness level. Walking or running on a treadmill and breathing into a machine that measures oxygen level during test. Heart rhythm is continuously monitored during exercise using an electrocardiogram (ECG).<br>Diagnostic Test: Strength Test<br>* Measure the strength of leg muscles by kicking against a machine with resistance.<br>Diagnostic Test: Dual-Energy X-Ray Absorptiometry<br>* Body composition measurement.<br>* Other names: DEXA;Procedure: Muscle Biopsy<br>* Obtain a small piece of muscles from the upper part of the legs<br>Procedure: Fat Biopsy<br>* Fat sample taken from abdomen<br>Diagnostic Test: Resting Energy Expenditure<br>* Measured by indirect calorimetry. Measures how much energy the body uses at rest by placing a special plastic dome over the head while resting quietly for 30 minutes. Measures oxygen breathed in and carbon dioxide breathed out.<br>* Other names: REE;Diagnostic Test: Magnetic resonance imaging<br>* MRI on upper leg to look at fat and muscle<br>* Other names: MRI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle protein synthesis | Skeletal muscle protein synthesis will be measured from the rate of incorporation of infused amino acids measured by mass spectrometry. | Baseline, post-exercise approximately 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mRNA expression of exercise responsive genes | Measure messenger ribonucleic acids (mRNAs) expression on exercise responsive genes | Baseline, post-exercise approximately 8 hours | 
| Change in expression and activation (phosphorylation) of signaling proteins | Phosphorylation is a common mechanism for the regulation of receptor function | Baseline, post-exercise approximately 8 hours |