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).
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.
Study Type
OBSERVATIONAL
Women undergoing laparoscopic oophorectomy surgery ('surgical menopause') will be enrolled at Pennington Biomedical.
Women undergoing gonadal suppression via leuprolide acetate (Lupron \[AbbVie Inc.\]) will be enrolled at the University of Colorado-Denver.
Pennington Biomedical Research Center
Baton Rouge, Louisiana, United States
Rate of in vivo adipogenesis (via deuterium-enrichment of adipose tissue DNA)
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.
Time frame: Change from baseline in enrichment of DNA of adipose cells with deuterium at 8 weeks
Size of adipocytes
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).
Time frame: Change from baseline in size of adipocytes at 8 weeks post-surgery
Number of adipocytes
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.
Time frame: Change from baseline in number of adipocytes at 8 weeks post-surgery
Body composition (by Dual-energy X-ray Absorptiometry (DXA))
Fat mass, fat-free mass, and percent body fat will be assessed using a whole-body scanner GE iDXA.
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Time frame: Change from baseline in body composition at 8 weeks post-surgery
Adipose tissue gene and protein expression
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.
Time frame: Changes from baseline in gene and protein expression at 8 weeks post-surgery