Training Induced Muscle-Adipose EV Communication

NCT07106450 | Not Yet Recruiting DMC

• 2 other identifiers: P20GM156679-Prj5P20GM156679
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prediabetes

Keywords

muscle; extracellular vesicles; adipose

Outcome Measures

Primary Outcomes (2)

• 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

  60 minutes post-exercise (single measurement)

• 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.

  24-48 hours post-isolation (in vitro culture)

Secondary Outcomes (4)

• Serum extracellular vesicle miR-1 content

  Baseline, 0, 30, 60, and 90 minutes post-exercise

• Adipose tissue transcriptomic signatures

  60 minutes post-exercise (single measurement)

• Adrenergic receptor gene expression in adipose tissue

  60 minutes post-exercise (single measurement)

• Primary muscle miR-1 transcript levels

  60 minutes post-exercise (single measurement)

Other Outcomes (3)

• Extracellular vesicle tetraspanin marker profiles using ExoView platform

  Baseline and 90 minutes post-exercise

• Circulating extracellular vesicle count using ExoView single vesicle analysis platform

  Baseline and 90 minutes post-exercise

• Extracellular vesicle size distribution using ExoView single vesicle analysis

  Baseline and 90 minutes post-exercise

Study Arms (1)

Acute Resistance Exercise

EXPERIMENTAL

Participants will perform four exercises: squat, knee extension, leg press, and lat pulldown at 80% of 1-RM (repetition maximum) determined during a previous visit.

Behavioral: Acute Resistance Exercise

Interventions

Acute Resistance Exercise BEHAVIORAL

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).

Also known as: Strength Training

Acute Resistance Exercise

Eligibility Criteria

• Age: 30 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• For Prediabetic Group: BMI \> 30 kg/m², at least 3 features of metabolic syndrome including prediabetes (defined as fasting plasma glucose 100-125 mg/dL OR 2-hour post-load glucose on 75g OGTT 140-199 mg/dL OR HbA1C 5.7-6.4%)

You may not qualify if:

• 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
• Use of medications that significantly affect glucose metabolism or exercise response
• Active participation in structured exercise programs (\>1 day/week) within 3 months of enrollment
• Inability to safely participate in resistance exercise protocol

Sponsors & Collaborators

• Yuan Wen: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

University of Kentucky

Lexington, Kentucky, 40506, United States

Location

MeSH Terms

Conditions

Prediabetic State

Interventions

Resistance Training

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Yuan Wen, MD, PhD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuan Wen, MD/PhD

CONTACT

18592187185; ywen2@uky.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 22, 2025
• First Posted: August 6, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: March 23, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)