Training Induced Muscle Exosome Release (TIMER)

Muscle-derived Extracellular Vesicles and Their Interactions With Adipocytes in Human Metabolic Dysfunction

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.

Study Overview

• Status: Completed
• Conditions: Metabolism
• Intervention / Treatment: Behavioral: Acute Resistance Exercise

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University Of Kentucky

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acute Resistance Exercise; 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; 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).; Other Names: Strength Training

What is the study measuring?

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.	90 minutes

Collaborators and Investigators

• Sponsor: Yuan Wen
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: John McCarthy, Ph.D., University Of Kentucky; Principal Investigator: Yuan Wen, Ph.D., University Of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2019
• Primary Completion (Actual): November 30, 2022
• Study Completion (Actual): November 30, 2022

Study Registration Dates

• First Submitted: July 29, 2020
• First Submitted That Met QC Criteria: August 3, 2020
• First Posted (Actual): August 5, 2020

Study Record Updates

• Last Update Posted (Estimated): January 14, 2026
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Metabolism; Muscle; Resistance Exercise; Exosomes; Extracellular Vesicles
• Additional Relevant MeSH Terms: Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Therapeutics; Physical Therapy Modalities; Patient Care; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Physical Conditioning, Human; Exercise; Resistance Training
• Other Study ID Numbers: 43910; 3R01DK119619-02S1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No