A Study of Adipose Tissue in Adaptive Responses to Exercise

Sponsor

Mayo Clinic (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06053125

Collaborator

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

Enrollment

Location

Arms

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Obesity	Procedure: Adipose Tissue Biopsy Behavioral: Exercise	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

The Role of Adipose Tissue in Adaptive Responses to Exercise

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2026

Anticipated Study Completion Date :

Oct 1, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Adipose Immune Cell Populations [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.
Inflammatory proteins secreted from adipose tissue measured using the Olink Target Inflammation Panel (includes 96 inflammation-associated proteins) [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.
Adipose tissue macrophage populations [Pre-exercise, immediately post-exercise, and 3 hours after exercise]
Numbers of macrophages in the adipose tissue will be assessed by immunohistochemistry.
Adipose tissue gene expression of interleukin (IL)-6 measured by polymerase chain reaction (PCR). [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.
Adipose tissue gene expression of interleukin (IL)-8 measured by PCR. [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.
Adipose tissue gene expression of cluster of differentiation 68 (CD68) measured by PCR. [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.
Adipose tissue gene expression of cluster of differentiation 163 (CD163) measured by PCR. [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.
Adipose tissue gene expression of cluster of differentiation 206 (CD206) measured by PCR. [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.
Adipose tissue gene expression of adhesion G-protein coupled receptor E (ADGRE) measured by PCR. [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.
Adipose tissue gene expression of inducible nitric oxide synthase (INOS) measured by PCR. [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.
Adipose tissue gene expression of monocyte chemoattractant protein-1 (MCP1) measured by PCR. [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.
Adipose tissue gene expression of tumor necrosis factor alpha (TNFa) measured by PCR. [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.
Adipose tissue gene expression of leptin (LEPD) measured by PCR. [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.
Adipose tissue gene expression of adiponectin (ADIPOQ) measured by PCR. [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.
Inflammatory proteins found in adipose tissue measured using the Olink Target Inflammation Panel (includes 96 inflammation-associated proteins) [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.
Protein cargo of adipose extracellular vesicles measured using mass spectrometry [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).

Secondary Outcome Measures

Adipocyte cell size [Pre-exercise, immediately post-exercise, and 3 hours after exercise]
Adipocyte cell size will be determined using methylene blue staining and microscopy.
Plasma inflammatory cytokine concentrations measured using the Olink Target Inflammation Panel (includes 96 inflammation-associated proteins) [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.
Protein cargo of plasma extracellular vesicles measured using mass spectrometry extracellular vesicles [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).

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Obese (BMI 30-50 kg/m2) older (65-85 years) adults.
Normal weight (BMI 18.5-28 kg/m^2) older adults.
Obese young adults (18-35 years).
Normal weight young adults will be recruited.
Participants will be weight-stable (≥ 3 months).
Sedentary men and women.

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

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

Investigators

Principal Investigator: Hawley Kunz, PhD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Mayo Clinic Clinical Trials

Publications

None provided.

Responsible Party:

Hawley E. Kunz, Principal Investigator, Mayo Clinic

ClinicalTrials.gov Identifier:

NCT06053125

Other Study ID Numbers:

23-002049
K01DK134765

First Posted:

Sep 25, 2023

Last Update Posted:

Sep 25, 2023

Last Verified:

Sep 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Hawley E. Kunz, Principal Investigator, Mayo Clinic

exercise

adipose

cytokines

Study Results

No Results Posted as of Sep 25, 2023