A Study of Adipose Tissue in Adaptive Responses to Exercise

Healthy Clinical Trial

Official title:

The Role of Adipose Tissue in Adaptive Responses to Exercise

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06053125
• Other study ID #: 23-002049
• Secondary ID: K01DK134765
• Status: Recruiting
• Phase: N/A
• Start date: November 9, 2023
• Est. completion date: October 2026

Study information

• Verified date: December 2023
• Source: Mayo Clinic
• Contact: Rose Decker
• Phone: 507-255-6770
• Email: bilderback.rose[@]mayo.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: October 2026
• Est. primary completion date: October 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy
• Obesity

Intervention

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

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Body fat percentage	Body fat percentage will be assessed using dual energy x-ray absorptiometry (DEXA).	Baseline
Other	Cardiorespiratory Fitness	Individual maximal oxygen consumption (VO2 max) will be assessed by indirect calorimetry during a graded exercise test	Baseline
Other	White blood count	White blood count with differential will be measured by the Mayo clinical lab.	Baseline
Other	Fasting plasma insulin	Plasma insulin will be measured by the Mayo Clinical Lab.	Baseline
Other	Fasting plasma glucose	Plasma glucose will be measured by the Mayo Clinical Lab.	Baseline
Other	Hemoglobin A1c (HbA1c)	HbA1c will be measured by the Mayo Clinical Lab.	Baseline
Primary	Adipose Immune Cell Populations	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
Primary	Inflammatory proteins secreted from adipose tissue measured using the Olink Target Inflammation Panel (includes 96 inflammation-associated proteins)	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
Primary	Adipose tissue macrophage populations	Numbers of macrophages in the adipose tissue will be assessed by immunohistochemistry.	Pre-exercise, immediately post-exercise, and 3 hours after exercise
Primary	Adipose tissue gene expression of interleukin (IL)-6 measured by polymerase chain reaction (PCR).	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
Primary	Adipose tissue gene expression of interleukin (IL)-8 measured by PCR.	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
Primary	Adipose tissue gene expression of cluster of differentiation 68 (CD68) measured by PCR.	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
Primary	Adipose tissue gene expression of cluster of differentiation 163 (CD163) measured by PCR.	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
Primary	Adipose tissue gene expression of cluster of differentiation 206 (CD206) measured by PCR.	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
Primary	Adipose tissue gene expression of adhesion G-protein coupled receptor E (ADGRE) measured by PCR.	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
Primary	Adipose tissue gene expression of inducible nitric oxide synthase (INOS) measured by PCR.	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
Primary	Adipose tissue gene expression of monocyte chemoattractant protein-1 (MCP1) measured by PCR.	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
Primary	Adipose tissue gene expression of tumor necrosis factor alpha (TNFa) measured by PCR.	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
Primary	Adipose tissue gene expression of leptin (LEPD) measured by PCR.	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
Primary	Adipose tissue gene expression of adiponectin (ADIPOQ) measured by PCR.	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
Primary	Inflammatory proteins found in adipose tissue measured using the Olink Target Inflammation Panel (includes 96 inflammation-associated proteins)	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
Primary	Protein cargo of adipose extracellular vesicles measured using mass spectrometry	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	Adipocyte cell size	Adipocyte cell size will be determined using methylene blue staining and microscopy.	Pre-exercise, immediately post-exercise, and 3 hours after exercise
Secondary	Plasma inflammatory cytokine concentrations measured using the Olink Target Inflammation Panel (includes 96 inflammation-associated proteins)	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
Secondary	Protein cargo of plasma extracellular vesicles measured using mass spectrometry extracellular vesicles	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

External Links

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