A Study of Adipose Tissue in Adaptive Responses to Exercise

December 1, 2023 updated by: Hawley E. Kunz, Mayo Clinic

The Role of Adipose Tissue in Adaptive Responses to Exercise

The purpose of this research is to determine how exercise affects fat (adipose) tissue and how changes to adipose tissue that occur during and after exercise might improve health in aging and obesity.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Adipose tissue has important endocrine functions that influence metabolic health. Early evidence shows that adipose adapts to physiological stress, including exercise. The objective here is to determine how exercise-induced alterations in adipose tissue cellular composition and endocrine signaling may contribute to the beneficial adaptations to exercise in aging and obesity.

Immune cell populations and inflammatory signatures will be assessed in subcutaneous abdominal adipose tissue biopsies collected from obese and normal weight young and older adults before, immediately after, and 3 hours after a 30-min bout of cycling exercise at 70% of maximal oxygen consumption (VO2max). Mass spectrometry, Olink targeted inflammation assays, and RNA sequencing will be used for full proteomic and transcriptomic characterization of the adipose tissue secretome (the proteins and molecules secreted from the adipose tissue) and the cargo of extracellular vesicles isolated from plasma and media collected from cultured human adipose tissue explants generated from each time point.

Overall, the primary hypothesis of the proposed work is that a single bout of exercise triggers transient changes in adipose tissue paracrine/endocrine signals and immune cellular composition. The investigators propose that these responses contribute to the beneficial effects of exercise locally and in distal tissues and that the cumulative effects of acute changes in adipose tissue likely contribute to the positive alterations in adipose tissue associated with exercise training.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Adults between the ages of 18-35 OR 65-85.
  • BMI <28 kg/m2 or BMI between 30 kg/m2 and 40 kg/m2
  • Weight stable (≥ 3 months)
  • Generally healthy

Exclusion Criteria:

  • Participation in ≥ 30 minutes of structured physical activity ≥ 2 days per week.
  • Smoking/tobacco use.
  • Alcohol/substance abuse.
  • Pregnancy and breastfeeding.
  • Anemia.
  • Abnormal renal function.
  • Blood clotting disorders.
  • Coronary artery disease.
  • Uncontrolled thyroid disease.
  • Liver disease.
  • Use of medications known to influence the main outcomes of the study.
  • Orthopedic problems that may be aggravated by exercise.
  • Chronic disease at the discretion of the investigators.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Older adults with obesity
Participants with a body mass index (BMI) between 30 and 40 and aged 65-85 years will have an adipose tissue biopsy taken from the abdomen before and after exercise.
Procedure: Adipose Tissue Biopsy
Fat sample collected from abdomen before exercise, immediately after exercise, and 3 hours after exercise
Behavioral: Exercise
30 minutes of exercise on a cycle ergometer exercise machine
Experimental: Older adults without obesity
Participants with a BMI between 18.5 and 28 and aged 65-85 years will have an adipose tissue biopsy taken from the abdomen before and after exercise.
Procedure: Adipose Tissue Biopsy
Fat sample collected from abdomen before exercise, immediately after exercise, and 3 hours after exercise
Behavioral: Exercise
30 minutes of exercise on a cycle ergometer exercise machine
Experimental: Young adults with obesity
Participants with a BMI between 30 and 40 and aged 18-35 years will have an adipose tissue biopsy taken from the abdomen before and after exercise.
Procedure: Adipose Tissue Biopsy
Fat sample collected from abdomen before exercise, immediately after exercise, and 3 hours after exercise
Behavioral: Exercise
30 minutes of exercise on a cycle ergometer exercise machine
Experimental: Young adults without obesity
Participants with a BMI between 18.5 and 28 and aged 18-35 years will have an adipose tissue biopsy taken from the abdomen before and after exercise.
Procedure: Adipose Tissue Biopsy
Fat sample collected from abdomen before exercise, immediately after exercise, and 3 hours after exercise
Behavioral: Exercise
30 minutes of exercise on a cycle ergometer exercise machine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adipose Immune Cell Populations
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
The numbers of lymphocytes, monocytes, macrophages, and natural killer (NK) cells in the adipose tissue will be assessed by flow cytometry.
Pre-exercise, immediately post-exercise, and 3 hours after exercise
Inflammatory proteins secreted from adipose tissue measured using the Olink Target Inflammation Panel (includes 96 inflammation-associated proteins)
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
The concentrations of 96 different inflammatory proteins (including various cytokines and adipokines) will be measured using the targeted inflammation Olink proximity extension assay panel in media obtained from cultured adipose tissue explants. Adipose tissue samples will be cultured for 3 hours, and the culture media will be removed for the assessment of 96 different secreted inflammatory proteins. The Olink assay measures all 96 proteins in a single assay and all are reported as normalized protein expression values.
Pre-exercise, immediately post-exercise, and 3 hours after exercise
Adipose tissue macrophage populations
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
Numbers of macrophages in the adipose tissue will be assessed by immunohistochemistry.
Pre-exercise, immediately post-exercise, and 3 hours after exercise
Adipose tissue gene expression of interleukin (IL)-6 measured by polymerase chain reaction (PCR).
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
Gene expression of the inflammatory cytokine IL-6 will be measured in adipose tissue samples using real time (RT)-PCR.
Pre-exercise, immediately post-exercise, and 3 hours after exercise
Adipose tissue gene expression of interleukin (IL)-8 measured by PCR.
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
Gene expression of the inflammatory cytokine IL-8 will be assessed in adipose tissue samples using real-time (RT)-PCR.
Pre-exercise, immediately post-exercise, and 3 hours after exercise
Adipose tissue gene expression of cluster of differentiation 68 (CD68) measured by PCR.
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
Gene expression of the macrophage marker CD68 be assessed in adipose tissue samples using real time (RT)-PCR.
Pre-exercise, immediately post-exercise, and 3 hours after exercise
Adipose tissue gene expression of cluster of differentiation 163 (CD163) measured by PCR.
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
Gene expression of the anti-inflammatory macrophage marker CD163 will be assessed in adipose tissue samples using RT-PCR.
Pre-exercise, immediately post-exercise, and 3 hours after exercise
Adipose tissue gene expression of cluster of differentiation 206 (CD206) measured by PCR.
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
Gene expression of the anti-inflammatory macrophage marker CD206 will be assessed in adipose tissue samples using RT-PCR.
Pre-exercise, immediately post-exercise, and 3 hours after exercise
Adipose tissue gene expression of adhesion G-protein coupled receptor E (ADGRE) measured by PCR.
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
Gene expression of the macrophage marker ADGRE will be assessed in adipose tissue samples using RT-PCR.
Pre-exercise, immediately post-exercise, and 3 hours after exercise
Adipose tissue gene expression of inducible nitric oxide synthase (INOS) measured by PCR.
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
Gene expression of the pro-inflammatory macrophage marker INOS will be assessed in adipose tissue samples using RT-PCR.
Pre-exercise, immediately post-exercise, and 3 hours after exercise
Adipose tissue gene expression of monocyte chemoattractant protein-1 (MCP1) measured by PCR.
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
Gene expression of the inflammatory cytokine MCP1 will be assessed in adipose tissue samples using RT-PCR.
Pre-exercise, immediately post-exercise, and 3 hours after exercise
Adipose tissue gene expression of tumor necrosis factor alpha (TNFa) measured by PCR.
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
Gene expression of the inflammatory cytokine TNFa will be assessed in adipose tissue samples using RT-PCR.
Pre-exercise, immediately post-exercise, and 3 hours after exercise
Adipose tissue gene expression of leptin (LEPD) measured by PCR.
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
Gene expression of the pro-inflammatory adipokine LEPD will be assessed in adipose tissue samples using RT-PCR.
Pre-exercise, immediately post-exercise, and 3 hours after exercise
Adipose tissue gene expression of adiponectin (ADIPOQ) measured by PCR.
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
Gene expression of the anti-inflammatory adipokine ADIPOQ will be assessed in adipose tissue samples using RT-PCR.
Pre-exercise, immediately post-exercise, and 3 hours after exercise
Inflammatory proteins found in adipose tissue measured using the Olink Target Inflammation Panel (includes 96 inflammation-associated proteins)
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
The concentrations of 96 different inflammatory proteins (including various cytokines and adipokines) will be measured in adipose tissue lysates using the targeted inflammation Olink proximity extension assay panel. This assay measures all 96 proteins in a single assay and all are reported as normalized protein expression values.
Pre-exercise, immediately post-exercise, and 3 hours after exercise
Protein cargo of adipose extracellular vesicles measured using mass spectrometry
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
Adipose tissue samples will be cultured for 3 hours, and the culture media will be removed. From this media, extracellular vesicles will be isolated. In these extracellular vesicles, mass spectrometry will be performed to examine the entire proteome (all proteins) contained within these extracellular vesicles. Using the large number of proteins identified, the investigators will examine changes in categories of protein types (e.g., inflammatory proteins, metabolic proteins, transcriptional proteins).
Pre-exercise, immediately post-exercise, and 3 hours after exercise

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adipocyte cell size
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
Adipocyte cell size will be determined using methylene blue staining and microscopy.
Pre-exercise, immediately post-exercise, and 3 hours after exercise
Plasma inflammatory cytokine concentrations measured using the Olink Target Inflammation Panel (includes 96 inflammation-associated proteins)
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
The concentrations of 96 different inflammatory proteins (including various cytokines and adipokines) will be measured in plasma samples using the targeted inflammation Olink proximity extension assay panel. This assay measures all 96 proteins in a single assay and all are reported as normalized protein expression values.
Pre-exercise, immediately post-exercise, and 3 hours after exercise
Protein cargo of plasma extracellular vesicles measured using mass spectrometry extracellular vesicles
Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise
Extracellular vesicles will be isolated from plasma samples. In these extracellular vesicles, mass spectrometry will be performed to examine the entire proteome (all proteins) contained within these extracellular vesicles. Using the large number of proteins identified, the investigators will examine changes in categories of protein types (e.g., inflammatory proteins, metabolic proteins, transcriptional proteins).
Pre-exercise, immediately post-exercise, and 3 hours after exercise

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Body fat percentage
Time Frame: Baseline
Body fat percentage will be assessed using dual energy x-ray absorptiometry (DEXA).
Baseline
Cardiorespiratory Fitness
Time Frame: Baseline
Individual maximal oxygen consumption (VO2 max) will be assessed by indirect calorimetry during a graded exercise test
Baseline
White blood count
Time Frame: Baseline
White blood count with differential will be measured by the Mayo clinical lab.
Baseline
Fasting plasma insulin
Time Frame: Baseline
Plasma insulin will be measured by the Mayo Clinical Lab.
Baseline
Fasting plasma glucose
Time Frame: Baseline
Plasma glucose will be measured by the Mayo Clinical Lab.
Baseline
Hemoglobin A1c (HbA1c)
Time Frame: Baseline
HbA1c will be measured by the Mayo Clinical Lab.
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

  • Principal Investigator: Hawley Kunz, PhD, Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 9, 2023

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

October 1, 2026

Study Registration Dates

First Submitted

September 7, 2023

First Submitted That Met QC Criteria

September 19, 2023

First Posted (Actual)

September 25, 2023

Study Record Updates

Last Update Posted (Estimated)

December 5, 2023

Last Update Submitted That Met QC Criteria

December 1, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 23-002049
  • K01DK134765 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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