Clinical trial NCT04500769: Training Induced Muscle Exosome Release
Official title: Muscle-derived Extracellular Vesicles and Their Interactions With Adipocytes in Human Metabolic Dysfunction
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Metabolism
Keywords: Metabolism
Muscle
Extracellular Vesicles
Exosomes
Resistance Exercise
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2020-08-05
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: miR-1 Abundance
timeFrame: 90 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: John McCarthy, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Kentucky
name: Yuan Wen, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: