Myeloid to Adipocyte Transdifferentiation in Human Cells

NCT02654925 | Completed

• 2 other identifiers: 15-1779UL1TR001082
• Study Type: observational
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

In order to design new programs to help prevent weight gain, promote successful and sustainable weight loss, and help treat diseases related to obesity, the investigators need a better understanding of why accumulating fat in certain regions of the body is bad for health. It is known that not all fat cells are the same, but it was recently discovered that some fat cells may arise from stem cells that come from the bone marrow (bone marrow progenitors), a previously unrecognized origin. This discovery has been paradigm shifting, because dogma has long held that all white fat cells arise from fat tissue resident mesenchymal stem cells. This is also important because fat cells arising from the bone marrow lineage may be linked to worse health outcomes. The aim of this study is to determine if cells that were not previously believed to contribute to fat generation in humans are indeed capable of becoming fat cells. To answer this question the investigators will take samples of cells from the blood and the fat tissue of younger and older men and women, isolate the cells that came from the bone marrow and grow them in culture to determine if they will turn into fat cells. The results of this investigation may reveal potential mechanistic targets for future therapies to reduce the negative health outcomes associated with obesity related chronic diseases.

Conditions

Obesity

Outcome Measures

Primary Outcomes (2)

• Adipogenic potential as measured by Oil Red-O staining (quantification by absorbance).

  Within 60 days of biopsy

• Adipocyte specific gene expression will be measured by qPCR (quantitative polymerase chain reaction) to confirm adipocyte status.

  Sample collection within 60 days of biopsy, batched analysis completed depending on enrollment.

Secondary Outcomes (3)

• Assessment of the fraction of myeloid cells that become 'mesenchymal-like' (CD45-/CD14-/CD34+) (CD: cluster of differentiation) after fibrin culture by flow cytometry.

  Within 2 weeks of biopsy

• Progenitor cell proliferation capacity as measured by BrdU (bromodeoxyuridine) incorporation

  Within 60 days of biopsy

• In vivo adipogenesis in the Matrigel plug will be assessed by immunohistochemistry (IHC) for adipocyte (e.g., adiponectin) and nuclear markers (e.g., DAPI).

  Samples will be collected within 60 days of biopsy, batched sample analysis will occur dependent on subject enrollment

Study Arms (4)

Young Men

men 21-40 years of age

Procedure: Adipose Tissue Biopsy

Young Women

women 21-40 years of age; young women will be premenopausal and eumenorrheic, not on hormonal contraceptive therapy.

Procedure: Adipose Tissue Biopsy

Older Men

men 55-100 years of age

Procedure: Adipose Tissue Biopsy

Older Women

women 55-100 years of age; older women will be postmenopausal who are at least 12 months past the final menstrual period (FMP).

Procedure: Adipose Tissue Biopsy

Interventions

Adipose Tissue Biopsy PROCEDURE

Older Men; Older Women; Young Men; Young Women

Eligibility Criteria

• Age: 21 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Community sample

You may qualify if:

• Men and women age 21-40 y or 55-100 y;
• Older women will be postmenopausal who are at least 12 months past the final menstrual period (FMP);
• Young women will be premenopausal and eumenorrheic, not on hormonal contraceptive therapy;
• Body Mass Index (BMI) 22-35 kg/m2;
• Non-active to moderately active (vigorous exercise ≤ 3 days/wk lasting \< 30 min).

You may not qualify if:

• Immunosuppression therapy;
• On blood thinners, aspirin, or NSAIDs that cannot be withheld for the biopsy;
• Prior history of allergies to local anesthetics;
• Current use of hormones, or glucose lowering medication;
• Currently engaged in a vigorous exercise or diet program;
• Currently gaining or losing weight or using weight loss drugs;
• Type 2 diabetes (past/current diagnosis or treatment);
• Diagnosis of uncontrolled metabolic disorders (e.g., thyroid);
• History of severe obesity BMI ≥ 40 or significant weight loss (≥ 50 lbs);
• Postmenopausal - hormonal menopausal therapy use currently or in the previous 6 months;
• Premenopausal - irregular menstrual cycles defined as 2 or more missed cycles in the previous year, pregnant or planning to become pregnant during the study timeline (urine pregnancy test will be performed before DEXA \[dual energy x-ray absorptiometry\] scan is completed).

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Kathleen M Gavin, PhD

  University of Colorado Denver Anschutz Medical Campus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2016
• First Posted: January 13, 2016
• Study Start: March 1, 2016
• Primary Completion: June 15, 2021
• Study Completion: June 15, 2021
• Last Updated: June 24, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)