# Diminished Sex Hormone Levels Stimulate Production of Inflammatory Bone Marrow-Derived Adipocytes

> **NIH VA I01** · VA EASTERN COLORADO HEALTH CARE SYSTEM · 2021 · —

## Abstract

Menopause is a normal occurrence in all women and a gradual process that begins in the 5th decade of
life. Menopause is characterized by the loss of ovarian hormones that ultimately leads to a number of
comorbidities including weight gain, redistribution of fat from hips, waist and buttocks to the abdomen, and
decreased metabolic activity. Female US military veterans are the fastest growing patient population in the
Veterans Administration Health Care system, and more than a third of those patients are pre-, post- or
currently menopausal. However, the mechanisms by which menopausal changes in ovarian hormone
production regulate body fat content and metabolism is an unexplored area in VA research.
 We have discovered a subpopulation of adipocytes in adipose depots of mice and humans generated
from hematopoietic stem cells, termed bone marrow-derived adipocytes (BMDA). These cells are produced in
numbers sufficient to influence adipose tissue function, and their production is increased by loss of gonadal
sex hormones in mouse models that mimic menopause in women. These observations were noteworthy
because BMDAs differ from conventional adipocytes and possess a potentially detrimental phenotype,
characterized by elevated production of inflammatory cytokines.
 Recent preliminary data demonstrates that BMDA are produced from adipose tissue stromal cells that
express both myeloid and mesenchymal marker that we have termed “myeloid adipocyte progenitors” or
MAPs. Since evidence supporting the proliferation of mature adipocytes remains controversial, the ability of
gonadal hormones to regulate BMDA abundance can be attributed to the production and/or proliferation of
MAPs. This project will test the hypothesis that estrogen and follicle stimulating hormone differentially
regulate the production of MAPs (and BMDAs), altering the cellular composition of adipose and
resulting in significant changes in metabolic and inflammatory phenotype. Three Specific Aims will test
this hypothesis by determining whether 1) ablation of ovarian hormone receptors, or 2) direct depletion of
ovarian hormones regulates BMDA abundance. A third aim will measure changes in body composition and
metabolic parameters in mice with depletion of MAPs and ovarian hormones.
 Successful completion of these studies has the potential to establish the crucial contribution of MAPs to
adipose tissue heterogeneity and changes to adipose tissue function with loss of ovarian hormone production.
A better understanding of this phenomenon will highlight opportunities to control the cellular composition and
function of adipose tissue as a novel strategy to combat menopausal comorbidities.

## Key facts

- **NIH application ID:** 10017066
- **Project number:** 1I01BX005135-01
- **Recipient organization:** VA EASTERN COLORADO HEALTH CARE SYSTEM
- **Principal Investigator:** Dwight J Klemm
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017066

## Citation

> US National Institutes of Health, RePORTER application 10017066, Diminished Sex Hormone Levels Stimulate Production of Inflammatory Bone Marrow-Derived Adipocytes (1I01BX005135-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10017066. Licensed CC0.

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