# Marrow Adipose Compartment Physiology in Caloric Restriction and Aging

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $342,100

## Abstract

ABSTRACT
Despite its association with low bone density and increased fracture risk, marrow adipose tissue
(MAT) remains poorly understood. MAT provides energy for exercise-induced bone anabolism in
a calorie-replete state. In the osteoporotic states of caloric restriction and aging, MAT's role may
differ. Our data shows MAT increases in CR in parallel to low bone-turnover and quantity. With
exercise, CR-MAT decreases, turnover increases, and bone loss occurs. CD36, a marker for fatty
acid uptake, increased in CR-bone, along with a diminution in markers of fatty acid mobilization
and β-oxidation, suggesting a decreased lipolytic capacity in CR-MAT. Thus, the CR-MAT depot
may be inaccessible, due to reduced metabolic capacity for lipolysis. In our two models of aging,
MAT increased; also, osteoclasts localized to MAT in aged mouse bones and bones showed
increased markers of resorption, inflammation, and mitochondrial biogenesis. We thus
hypothesize that in a calorie replete, non-aged condition, exercise depletes MAT in support of
bone anabolism; however, in CR, and possibly aging, exercise utilization of MAT supports bone
catabolism. In SA1, we will ask how MAT and bone respond to exercise during calorie restriction.
In SA2 we determine how MAT and bone respond to exercise during aging. This proposal uses
innovative techniques to quantify, localize and metabolically phenotype MAT. A reporter mouse
will be used to identify newly differentiated marrow adipocytes and characterize-at the cellular
level-whether MAT is increased due to lipid uptake or due to MSC lineage switch in CR. IN SA2,
a progeroid mouse model will be used in addition to physiologic aging to test the bone and MAT
response to exercise. Combining a volumetric MAT measure, adipocyte lineage tracing, histologic
and molecular analyses of MAT, metabolic capacity measures, as well as bone microarchitecture
via µCT, biomechanical testing and dynamic histomorphometry, positions us to answer
fundamental questions as to the metabolic function of MAT in the setting of both CR and aging,
and its relationship to bone health.

## Key facts

- **NIH application ID:** 9908052
- **Project number:** 5R01AR073264-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Maya Shalev Styner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $342,100
- **Award type:** 5
- **Project period:** 2019-04-05 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908052

## Citation

> US National Institutes of Health, RePORTER application 9908052, Marrow Adipose Compartment Physiology in Caloric Restriction and Aging (5R01AR073264-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9908052. Licensed CC0.

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