Adipose Tissue, Menopause, Microbiome
Conditions
Brief summary
This research study plans to learn more about the role of female sex hormones on adipose tissue (or fat) and the gut microbiome (or the organisms that are in your digestive tract). The rationale for this study is that the rate at which women gain fat (especially in the stomach region) increases after menopause. It is thought to be due to the loss of estrogen because post-menopausal women who take estrogen gain less weight than those who do not take estrogen. Gut bacteria process estrogen and help determine the types of estrogen that circulate in the body. These bacteria can be changed with lifestyle factors such as diet, and may therefore, also affect the risk of diseases that are more common in women after menopause i.e., cardiovascular disease and cancer. In this study the investigators will obtain fat biopsies before and after 6 months of ovarian hormone suppression to measure how the fat cells change with the loss of female sex hormones (e.g., medical menopause). The investigators will also obtain stool and urine samples before and every month during the study to measure changes in the microbiome.
Interventions
OTHERGnRHag
Ovarian Hormone Suppression - the purpose of the intervention is not to study the drug, but the impact of the loss of ovarian hormones.
Sponsors
University of Colorado, Denver
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Enrollment into the parent protocol (COMIRB 16-1479 - The impact of estrogen status on the biological function of brown adipose tissue in women measured using quantitative PET/CT; PI - Edward Melanson, PhD) * Participation in GnRHag intervention
Exclusion criteria
* Known allergy to lidocaine or other numbing medication * Uncontrolled bleeding disorder or inability to withhold aspirin/NSAIDs or other blood thinning medications for 7 days prior to biopsy procedure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Accumulation of Myeloid Cells | 8 months after enrollment of last participant | Quantification of accumulation of myeloid cells in abdominal subcutaneous adipose tissue of women before and after gonadal hormone suppression as assessed by CD45+/CD14+ staining via flow cytometry of isolated adipose stroma. |
| Progenitor proliferation and adipogenic potential | 1 year after completion of last participant | Progenitor proliferation measured by BrdU and adipogenic potential as measured by Oil Red-O staining with quantification by absorbance. Adipocyte specific gene/protein expression will be measured to confirm adipocyte status. |
| Gut microbial diversity | 1 year after completion of last participant | Comparison of gut microbial diversity before and after gonadal hormone suppression at monthly intervals as assessed by sequencing of the V4 region of 16s rRNA |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| In Vitro Metabolic Phenotyping | 2 years after completion of last participant | in vitro measurement of lipid and glucose uptake, insulin and adrenergic sensitivity, and mitochondrial content. |
| β-glucuronidase activity | 2 years after completion of last participant | analysis of β-glucuronidase activity in fecal samples from premenopausal women under gonadal hormone suppression therapy via a 96-well assay. This will serve as a direct measure of fecal capacity for estrogen metabolism. |
| Estrogen parent: metabolite ratios | 2 years after completion of last participant | comparison of estrogen parent: metabolite ratios in relation to changes in bacterial diversity and enzyme activity. We will use UPLC-MS/MS metabolomics. |
Countries
United States
Outcome results
None listed