# Sex differences in adipogenic potential of adipose tissue myeloid cells in humans

> **NIH NIH K01** · UNIVERSITY OF COLORADO DENVER · 2020 · $144,504

## Abstract

PROJECT SUMMARY/ABSTRACT
The overarching goal of this application is to provide Dr. Gavin the expertise and skills necessary to initiate
an independent research career in the field adipose tissue physiology, with a specific focus on defining the role
of sex and gonadal hormones in adipocyte development and phenotype. The importance of distinct
developmental pathways in adipocyte biology has been largely overlooked because dogma has held that new
adipocytes are derived from resident progenitor cells. Recent preclinical advances have revealed that new
adipocytes arise from a heterogeneous population of both resident and non-resident progenitor cells. Studies
in mice have shown that these non-resident progenitors arise from bone marrow-derived progenitor cells of
myeloid lineage (BMP-derived adipocytes). Importantly, we and others have provided evidence of BMP-derived
adipocytes in humans. BMP-derived adipocytes appear to have a gene expression pattern that is distinct from
white or brown adipocytes. This pattern is characterized by increased inflammatory factors and decreased
mitochondrial enzymes, implicating this adipocyte lineage as a potential contributor to the adverse metabolic
profile associated with excess adiposity. Preliminary evidence suggests that accumulation of BMP-derived
adipocytes is greater in female compared to male mice, and in ovariectomized compared to intact female mice.
Furthermore, the accumulation of these cells is increased in visceral depots. Collectively, these studies
suggest that gonadal hormone status is mechanistically linked with adipocyte development and the health risks
of excess adiposity. Accordingly, the global hypothesis of this project is that gonadal hormones regulate the
developmental pathway and metabolic phenotype of new adipocytes in women and men. Specifically, we
hypothesize that reduced gonadal steroid hormones favor the recruitment and differentiation of BMP-derived
adipocytes. To test these hypotheses, we will obtain subcutaneous abdominal adipose tissue biopsies from
women and men before and after gonadal hormone suppression. The stromal fraction will be isolated from
adipose tissue and sorted into populations of myeloid and mesenchymal cells by flow cytometry that will then
be grown in culture with and without exposure to gonadal hormones. The Specific Aims are to determine
whether 1) gonadal hormone status in women and men alters adipose tissue myeloid cell accumulation and
determines their ability to undergo mesenchymal transition in vitro and 2) gonadal hormone status and
progenitor lineage (myeloid versus conventional) regulate the proliferation, differentiation, metabolic
phenotype, and metabolomics profile of primary human adipocytes. An exploratory aim will be to compare
subcutaneous and visceral fat cells obtained from the same individuals undergoing abdominal surgery using
the methods proposed in Aims 1 and 2. If successful, our results will provide evidence that some adipocytes in
human...

## Key facts

- **NIH application ID:** 9947736
- **Project number:** 5K01DK109053-05
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Kathleen Marie Gavin
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $144,504
- **Award type:** 5
- **Project period:** 2016-09-16 → 2021-09-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9947736

## Citation

> US National Institutes of Health, RePORTER application 9947736, Sex differences in adipogenic potential of adipose tissue myeloid cells in humans (5K01DK109053-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9947736. Licensed CC0.

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