Training Induced Muscle Exosome Release

Study Overview
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Brief Summary
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The primary objective of this study is to quantify miR-1 release from muscle in extra-cellular vesicles following an acute resistance exercise bout and potential delivery to subcutaneous adipose tissue in young healthy and obese adults.

Detailed Description
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Numerous studies in humans and animals have shown that aerobic exercise is beneficial to adipose tissue function and whole-body metabolism. Both acute and chronic aerobic exercise enhance adipocyte catecholamine sensitivity in humans and animals. Although relatively few studies have investigated whether adipose adrenergic signaling is affected by resistance exercise (RE), it is known that a single bout of RE can increase circulating NEFA and resting energy expenditure and decrease respiratory quotient for up to 24 hours, indicative of increased adipocyte lipolysis and muscle fatty acid oxidation. Furthermore, the lipolytic response to RE is impaired in obese men. Using synergist ablation, a model of RE in mice, the investigators show that adipose transcriptional responses are exosome-dependent, and that serum exosomes enhance adipocyte catecholamine sensitivity and lipolysis for at least 24 hours. To the investigator's knowledge, this is the first demonstration of a potential mechanism whereby RE imparts metabolic adaptations in adipose. Since adipose metabolic function is crucial for determining whole-body metabolic outcomes, the ability of RE-induced exosomes to improve adipose metabolism has significant clinical implications.

Official Title
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Exercise-induced Skeletal Muscle Exosomes Promote Adipocyte Lipolysis

Conditions
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Metabolism

Intervention / Treatment
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* Behavioral: Acute Resistance Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-30 years of age. Either BMI <25 or >30. Relatively sedentary, reporting no participation in regular (>1 day per week) exercise for at least the past 3 months. Non-smoker. Exclusion Criteria: BMI between 25 and 30. Evidence or signs and symptoms for cardiovascular disease (previous heart attack, arrhythmias, angina, shortness of breath, extreme fatigue, unusual pain in neck, jaw, throat, upper abdomen, or back, swelling in feet, legs, or ankles). Evidence or signs and symptoms of metabolic syndrome or disorder (diagnosis of diabetes or insulin resistance, elevated BP, high fasting blood sugar, abnormal cholesterol or triglyceride levels). Chronic aspirin or NSAID use (unless it can be safely stopped prior to the biopsies), and any other use of an anticoagulant (e.g., Coumadin) or history of bleeding including history of hypo- or hyper-coagulation disorders. Neurological, musculoskeletal, or other disorder that would preclude safe participation in the weight lifting tasks and all performance tests. Any other medical condition that would interfere with testing or increase one's risk of complications during exercise, as judged by the study physician. Any other condition or events considered exclusionary by the PI and/or physician, such as non-compliance. Lidocaine allergy (1% lidocaine is the local anesthetic used during the muscle biopsy procedure). Pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 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: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acute Resistance Exercise<br>Participants will perform four exercises: squat, knee extension, leg press, and lat pulldown at 80% of 1-RM determined during a previous visit. | Behavioral: Acute Resistance Exercise<br>* Participants will perform three sets of eight repetitions, with a 90-120 second rest between sets, with a fourth set performed to failure. All resistance exercise will be performed on pneumatic resistance devices (Keiser Sports Health Equipment, Fresno, CA).<br>* Other names: Strength Training;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| miR-1 abundance | Exosomal, muscle, and adipose miR-1 abundance will be quantified at baseline and following an acute bout of resistance exercise by qPCR. Primary miR-1A/B abundance in muscle and adipose will also be quantified by qPCR. Mir-1 and primary miR-1A/B abundance will be normalized to U6 RNA or Rpl38 abundance,respectively, with normalized expression presented in arbitrary units. | 90 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metabolism, Muscle, Extracellular Vesicles, Exosomes, Resistance Exercise