Understanding the Roles of Hormones in Adipocyte Remodeling Following Menopause
- Conditions
- Menopause SurgicalHormone DeficiencyEstrogen DeficiencyAdiposityFollicle-Stimulating Hormone Deficiency
- Interventions
- Procedure: 'Surgical Menopause' GroupDrug: 'Drug-Induced Menopause' Group
- Registration Number
- NCT03856268
- Lead Sponsor
- Pennington Biomedical Research Center
- Brief Summary
The overarching aims of this study are to:
1. Characterize the rate of in vivo adipogenesis, and changes in adipose tissue gene and protein expression, in the scABD and scFEM depots of women undergoing surgical menopause (↓E2, ↑FSH).
2. Characterize the rate of in vivo adipogenesis, and changes in adipose tissue gene and protein expression, in the scABD and scFEM depots of women undergoing gonadal suppression (↓E2, ↓FSH).
- Detailed Description
This is a cross-sectional study where two groups of premenopausal women (ages 18-50 y) will be enrolled in a parallel arm study:
* Arm 1 (Surgical Menopause): up to 6 women undergoing laparoscopic, elective bilateral oophorectomy \[Site: Pennington Biomedical Research Center\].
* Arm 2 (Pharmacology-Induced Menopause): up to 6 women undergoing gonadal suppression via leuprolide acetate (Lupron \[AbbVie Inc.\]) \[Site: UC-Denver\].
We will compare each arm of women to non-oophorectomized, premenopausal women (controls) with normal menstrual cycles (Apple\&Pear study; NCT01748994; PI: Ravussin) selectively matched (1:2) for age and BMI. The Apple\&Pear study uses the same in vivo adipogenesis labeling protocol, with similar age and BMI criteria, as the proposed study.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- Female
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description ARM 1: 'Surgical Menopause' Group 'Surgical Menopause' Group Premenopausal women having an oophorectomy. ARM 2: "Drug-Induced Menopause' 'Drug-Induced Menopause' Group Premenopausal women with gonadal suppression
- Primary Outcome Measures
Name Time Method Rate of in vivo adipogenesis (via deuterium-enrichment of adipose tissue DNA) Change from baseline in enrichment of DNA of adipose cells with deuterium at 8 weeks Deuterium from the deuterium-labeled water is incorporated into the newly-synthesized DNA of newly-formed fat cell precursor cells through cell replication. The latter carry over the label when they become fat cells through differentiation. Enzymatic digestion of the fat tissue isolates the individual cells constituting the fat tissue. Centrifugation of the cell suspension allows the separation of fat cells into a floating layer and a pellet comprised of stromal-vascular cells including the fat cell precursor cells and small fat cells. As the fat cell precursor cells and small adipocytes have the property to attach quickly to plastic surfaces of culture dishes, a brief culturing of the stromal-vascular cells sorts these cells from the remaining cells. Thus, measuring the deuterium-enrichment of DNA from plastic-adherent stromal-vascular cells indicates the rate of in vivo formation of new mature fat cells and pre-adipocytes, a process collectively termed adipogenesis.
- Secondary Outcome Measures
Name Time Method Size of adipocytes Change from baseline in size of adipocytes at 8 weeks post-surgery Fat cell size will be determined using osmium fixation of the lipids and measurement of their diameter with Coulter Counter followed by calculation of fat cell volume. The mean lipid content of fat cells will be calculated by multiplying the fat cell volume by the density of triolein (0.915).
Body composition (by Dual-energy X-ray Absorptiometry (DXA)) Change from baseline in body composition at 8 weeks post-surgery Fat mass, fat-free mass, and percent body fat will be assessed using a whole-body scanner GE iDXA.
Number of adipocytes Change from baseline in number of adipocytes at 8 weeks post-surgery Fat cell number will be estimated by dividing the volume of adipose tissue depot of interest to the mean fat cell volume or the fat mass of the depot to the mean lipid content in fat cell.
Adipose tissue gene and protein expression Changes from baseline in gene and protein expression at 8 weeks post-surgery Expression levels of genes and proteins involved in adipocyte expansion and function (ERα, PPARγ2, C/EBPα, aromatase, adiponectin, and LPL), extracellular matrix remodeling and fibrosis (COL6(a1, a2, a3), COL4a1, and TGFβ), and inflammation (IL-6 and TNFα) will be assessed.
Trial Locations
- Locations (1)
Pennington Biomedical Research Center
🇺🇸Baton Rouge, Louisiana, United States