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A Study of Adipose Tissue in Adaptive Responses to Exercise

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ClinicalTrials.gov Identifier: NCT06053125
Recruitment Status : Recruiting
First Posted : September 25, 2023
Last Update Posted : October 5, 2023
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Hawley E. Kunz, Mayo Clinic

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 Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Study Start Date : November 2023
Estimated Primary Completion Date : October 2026
Estimated Study Completion Date : October 2026

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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).


Other Outcome Measures:
  1. Body fat percentage [ Time Frame: Baseline ]
    Body fat percentage will be assessed using dual energy x-ray absorptiometry (DEXA).

  2. Cardiorespiratory Fitness [ Time Frame: Baseline ]
    Individual maximal oxygen consumption (VO2 max) will be assessed by indirect calorimetry during a graded exercise test

  3. White blood count [ Time Frame: Baseline ]
    White blood count with differential will be measured by the Mayo clinical lab.

  4. Fasting plasma insulin [ Time Frame: Baseline ]
    Plasma insulin will be measured by the Mayo Clinical Lab.

  5. Fasting plasma glucose [ Time Frame: Baseline ]
    Plasma glucose will be measured by the Mayo Clinical Lab.

  6. Hemoglobin A1c (HbA1c) [ Time Frame: Baseline ]
    HbA1c will be measured by the Mayo Clinical Lab.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06053125


Contacts
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Contact: Rose Decker 507-255-6770 bilderback.rose@mayo.edu

Locations
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United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Hawley Hunz, PhD    507-255-2061    Kunz.Hawley@mayo.edu   
Contact: Rose McCain    507-255-6770    bilderback.rose@mayo.edu   
Sponsors and Collaborators
Mayo Clinic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Hawley Kunz, PhD Mayo Clinic
Additional Information:
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Responsible Party: Hawley E. Kunz, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT06053125    
Other Study ID Numbers: 23-002049
K01DK134765 ( U.S. NIH Grant/Contract )
First Posted: September 25, 2023    Key Record Dates
Last Update Posted: October 5, 2023
Last Verified: October 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hawley E. Kunz, Mayo Clinic:
exercise
adipose
cytokines