# Brown Adipose Tissue and Cardioprotection

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $391,117

## Abstract

Abstract
While the thermogenic properties of brown adipose tissue (BAT) are well known, we recently reported
previously unknown cardioprotective properties of BAT against catecholamine-induced myocardial injury. In
preliminary studies that support the present proposal, we identified bone morphogenetic protein 3b (BMP-
3b) as a cardioprotective adipokine that may mediate BAT-related cardioprotection. The objective of this
proposal is to further investigate the cardioprotective effects of BAT and BMP-3b in a murine model of
myocardial ischemia-reperfusion (I/R) injury. In preliminary studies, we demonstrated that mice that are
deficient in the uncoupling protein 1 (UCP1), a protein synthetized by BAT and required for BAT thermogenic
function, develop greater myocardial infarction (MI) size than WT mice after I/R injury. We identified BMP-3b, a
protein of previously unknown cardiovascular properties, as an adipokine synthesized and secreted by the
activated BAT of WT but not of UCP1-deficient mice. We demonstrated that BMP-3b treatment decreased MI
size after I/R injury in WT mice. In preliminary studies, BMP-3b increased the levels of P-Smad1/5/8 and
S1177P-NOS3, and decreased apoptosis in serum-deprived cardiomyocytes (CMs). Furthermore, BMP-3b
increased left ventricular (LV) P-Smad1/5/8 and STAT3 levels after I/R. To further investigate the
cardioprotective role of BAT in I/R injury, we will determine whether restoring functional BAT in UCP1-/- mice
and increasing functional BAT in WT mice limit MI size. In these studies, we will transplant BAT from WT mice
into UCP1-/- and WT mice prior to myocardial injury. By studying BMP-3b-/- and BAT-specific BMP-3b-/- mice,
we will elucidate whether BMP-3b is the adipokine in BAT, and BAT the BMP-3b producing tissue that is
required to limit I/R injury. To investigate the mechanisms underlying the cardioprotective effects of BMP-3b,
the role of the BMP, NOS3 and STAT3 pathways in the cardioprotective effect of BMP-3b will be assessed
using both isolated mouse adult CMs and the in vivo I/R murine model. The CM receptors engaged by BMP-3b
will be identified. As a first step toward applying the results to humans, we will investigate whether BMP-3b is
secreted by human brown adipocytes, and whether myocardial infarction increases BMP-3b in the plasma of
human patients. To further investigate the potential clinical applicability of BMP-3b treatment in I/R injury, we
will test the effect of varying BMP-3b dose, and time of delivery relative to onset of injury, on the extent of
myocardial damage in the in vivo murine I/R model. Successful completion of these aims will define and
elucidate a novel cardioprotective effect of BAT in myocardial I/R injury and will characterize a previously
unknown cardioprotective adipokine secreted by BAT, BMP-3b. The proposal is a first step toward identifying
new cardioprotective therapies that may decrease myocardial I/R injury.

## Key facts

- **NIH application ID:** 9981487
- **Project number:** 5R01HL131613-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** MARIELLE SCHERRER-CROSBIE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,117
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981487

## Citation

> US National Institutes of Health, RePORTER application 9981487, Brown Adipose Tissue and Cardioprotection (5R01HL131613-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9981487. Licensed CC0.

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