# Mechanisms by Which Bone Marrow Adipose Tissue Expands During Calorie Restriction

> **NIH NIH F32** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $34,281

## Abstract

Project Summary
 Adipose tissue is located throughout the body, and adipocytes can have very unique
functions depending on the niche in which they reside. One understudied type of adipose tissue
is bone marrow adipose tissue (BMAT), which is located inside the bone as part of the bone
marrow. BMAT can make up to 70% of the bone marrow volume and is ~10% of total adipose
mass; however, very little is known about the function of these cells. BMAT is highly dynamic and
expands under a variety of conditions, including obesity, diabetes, osteoporosis, aging, estrogen
deficiency, anorexia, and calorie restriction (CR). The mechanism by which BMAT expands and
the role of BMAT expansion in whole-body physiology is poorly understood.
 We are particularly interested in BMAT expansion following CR because it is a situation in
which most other types of adipose tissue decrease in mass. Our goals are to understand why
BMAT responds differently than other types of adipose tissue following CR, determine the
physiological importance of this expansion, and identify what signals drive BMAT expansion. One
potential mechanism by which BMAT expands during CR, is through excess glucocorticoids.
Several conditions involving excess circulating glucocorticoids, such as Cushing’s Disease, have
been shown to also cause increased BMAT volume. Similarly, in healthy patients, BMAT volume
increases following injection of synthetic glucocorticoids. Therefore, we have designed a series
of experiments to test the overall hypothesis that following CR, BMAT plays an important role in
physiological adaptation and that excess glucocorticoids drive BMAT expansion by altering BMAT
gene expression.
 The field of BMAT biology has been limited by the ability to purify and manipulate bone
marrow adipocytes (BMA), while avoiding all other cell types within the bone marrow niche. To
test our hypothesis, we have developed a series of novel mouse models to selectively measure
gene expression and delete genes of interest within BMA. We will use these models to measure
gene expression in BMA compared to adipocytes from other adipose depots following CR using
single-nuclei RNA-sequencing. Additionally, we will target the primary mechanism of
glucocorticoid action, the glucocorticoid receptor, for deletion within BMA. We have also
developed models to measure how complete ablation of BMA impacts whole-body physiology.
Our results will provide a better understanding of BMAT’s physiological role, both at baseline and
following CR, and will potentially identify new therapeutic approaches to target BMAT for a
variety of metabolic diseases.

## Key facts

- **NIH application ID:** 10439959
- **Project number:** 3F32DK123887-02S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Rebecca L. Schill
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $34,281
- **Award type:** 3
- **Project period:** 2019-09-04 → 2022-03-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10439959

## Citation

> US National Institutes of Health, RePORTER application 10439959, Mechanisms by Which Bone Marrow Adipose Tissue Expands During Calorie Restriction (3F32DK123887-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10439959. Licensed CC0.

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