Training Induced Muscle-Adipose EV Communication
ConditionPrediabetes
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age30-55
SponsorYuan Wen
About this trial
This study examines how muscle cells communicate with fat cells through tiny packages called extracellular vesicles (EV) during exercise. These vesicles carry important molecules that may affect how the body processes sugar and fat. The research team observed significant variability in the adipose response to exercise, and used this variability to gain further insight into the mechanism through which mature microRNA-1 (miR-1) changes in adipose tissue. The investigators selected six subjects with the highest increase in miR-1 abundance in adipose tissue after exercise and compared them with the six subjects that had the most dramatic decrease in miR-1 abundance after exercise. The research team observed that participants intrinsically vary in their ability to endocytose EV into adipose tissue. It is unclear whether this variance in receptivity is a cause or consequence of the significant difference in EV-delivery of miR-1 to adipose tissue.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Age 30-55 years
Sedentary lifestyle (exercise <1 day/week for at least 3 months prior to enrollment)
Able to provide informed consent
For Control Group: BMI < 27 kg/m², normal glucose tolerance, no more than 1 feature of metabolic syndrome
Disqualifiers
Pregnancy (confirmed by pregnancy test in women of childbearing potential)
Type 2 diabetes mellitus
Cardiovascular contraindications to resistance exercise
Medical conditions that would interfere with muscle or adipose tissue biopsy procedures
Trial design
Design model
Single group
Treatments tested in this trial
Acute Resistance Exercise
BehavioralParticipants 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).
Treatment groups
40 Participants
are divided into 1 treatment groupGroup A: Acute Resistance ExerciseExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
miR-1 abundance in adipose tissue
Quantification of mature microRNA-1 levels in subcutaneous adipose tissue biopsies using quantitative Real Time-PCR as validated biomarker of in vivo extracellular vesicle uptake
Time frame
60 minutes post-exercise (single measurement)2
Extracellular vesicle uptake capacity in primary adipocytes
Measurement of fluorescently-labeled extracellular vesicle internalization in cultured primary adipocytes using confocal microscopy to quantify uptake rates in units of vesicles per minute per cell.
Time frame
24-48 hours post-isolation (in vitro culture)Secondary outcomes
1
Serum extracellular vesicle miR-1 content
Time-course analysis of microRNA-1 abundance in isolated serum extracellular vesicles using quantitative RT-PCR to track temporal dynamics of muscle-derived vesicle release
Time frame
Baseline, 0, 30, 60, and 90 minutes post-exercise2
Adipose tissue transcriptomic signatures
RNA-sequencing analysis of subcutaneous adipose tissue to identify differential gene expression patterns associated with high versus low extracellular vesicle uptake capacity, focusing on endocytotic pathways
Time frame
60 minutes post-exercise (single measurement)3
Adrenergic receptor gene expression in adipose tissue
Quantitative RT-PCR measurement of ADRβ1, ADRβ2, and ADRβ3 receptor mRNA levels in subcutaneous adipose tissue as downstream targets of miR-1 delivery
Time frame
60 minutes post-exercise (single measurement)4
Primary muscle miR-1 transcript levels
Quantification of pri-miR-1a and pri-miR-1b primary transcript abundance in vastus lateralis muscle biopsies using quantitative RT-PCR to assess exercise-induced miR-1 biogenesis
Time frame
60 minutes post-exercise (single measurement)Other outcomes
1
Extracellular vesicle tetraspanin marker profiles using ExoView platform
Characterization of circulating extracellular vesicle subpopulations based on surface tetraspanin protein expression (CD63, CD81, CD9) using ExoView R100 platform immunofluorescence detection and high resolution imaging. Units of Measure: Percentage of total vesicles positive for each marker.
Time frame
Baseline and 90 minutes post-exercise2
Circulating extracellular vesicle count using ExoView single vesicle analysis platform
Total number of circulating extracellular vesicles quantified using the ExoView R100 platform single vesicle analysis technology with tetraspanin capture antibodies (CD63, CD81, CD9). Units of Measure: Particles per milliliter
Time frame
Baseline and 90 minutes post-exercise3
Extracellular vesicle size distribution using ExoView single vesicle analysis
Size characterization of individual circulating extracellular vesicles measured using ExoView R100 platform automated analysis. Units of Measure: Nanometers (diameter).
Time frame
Baseline and 90 minutes post-exerciseSponsors and contacts
Click on the lead sponsor to view all of their trials.
Yuan Wen
Lead sponsor
University of Kentucky
Sponsor institution
National Institute of General Medical Sciences (NIGMS)
Collaborator
Source ClinicalTrials.gov
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