Metabolism
Conditions
Keywords
Metabolism, Muscle, Extracellular Vesicles, Exosomes, Resistance Exercise
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.
Interventions
BEHAVIORALAcute 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).
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Yuan Wen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| miR-1 Abundance | 90 minutes | Exosomal, muscle, and adipose miR-1 abundance will be quantified at baseline and following an acute bout of resistance exercise by qPCR. |
Countries
United States
Participant flow
Recruitment details
Subjects were actively recruited from the University of Kentucky campus as well as from the surrounding Lexington community through local advertisement using IRB approved recruitment flyers or newspaper advertisement. Recruitment occurred between March of 2019 and November 2022.
Pre-assignment details
Consent and baseline assessments were conducted prior to the resistance exercise intervention. Baseline assessments included demographics, medications, personal health and medical history, vitals, and physical activity readiness. Baseline assessment of strength was also conducted for each resistance exercise so that relative intensity could be standardized for each participant. All participants completed the same resistance exercise bout.
Participants by arm
| Arm | Count |
|---|---|
| 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.
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). | 38 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Acute Resistance Exercise |
|---|---|
| Age, Continuous | 28.71 years STANDARD_DEVIATION 5.99 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Region of Enrollment United States | 38 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 38 |
| other Total, other adverse events | 12 / 38 |
| serious Total, serious adverse events | 0 / 38 |
Outcome results
Primary
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.
Time frame: 90 minutes
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acute Resistance Exercise | miR-1 Abundance | Percent change in serum EV miR-1 with exercise | 226 percent change | Standard Deviation 313 |
| Acute Resistance Exercise | miR-1 Abundance | Percent change in muscle miR-1 with exercise | 110 percent change | Standard Deviation 82 |
| Acute Resistance Exercise | miR-1 Abundance | Percent change in adipose miR-1 with exercise | 286 percent change | Standard Deviation 464 |