# Genetic and Functional Investigation of Supraclavicular Brown Adipose Tissue

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $350,000

## Abstract

Obesity, which occurs when energy intake exceeds energy expenditure, is a major contributor to the
development of type II diabetes and cardiovascular disease. One significant form of energy expenditure is
nonshivering thermogenesis, the dissipation of chemical energy as heat by brown adipose tissue (BAT). The
recent rediscovery of BAT in the supraclavicular region in healthy human adults suggests that therapeutic
strategies utilizing BAT function could combat obesity and its related metabolic complications in humans. To
utilize BAT as a therapeutic tool, we first need to understand how supraclavicular BAT (scBAT) forms and
functions using a faithful animal model for human scBAT. We recently identified a mouse scBAT depot that
anatomically and molecularly resembles the supraclavicular depot found in humans. New preliminary studies
traced the lineage giving rise to scBAT to cardiac progenitor cells in the anterior heart field (AHF) that express
Myocyte enhancer factor 2c (Mef2c), revealing a lineage relationship between scBAT and the heart.
Knockdown of the Mef2c transcription factor in supraclavicular brown preadipocytes led to the loss of key
brown adipogenesis regulators, while selective ablation of scBAT perturbed metabolic homeostasis in healthy
chow-fed mice. Together, these findings led us to hypothesize that scBAT is a highly active metabolic BAT
depot that originates from cardiac progenitor cells in the anterior heart field and is dependent on Mef2c for
the regulation of its metabolic function. For specific aim 1, we will determine the developmental origin of
scBAT by determining if polypotent cardiac progenitor cells can be directly induced to become brown
adipocytes, analyzing scBAT for tissue defects after genetic ablation of Mef2c-AHF+ cells, and identifying cell
surface markers specific for supraclavicular brown adipocyte progenitors. For specific aim 2, we will
determine the role of Mef2c in the regulation of metabolic function of scBAT. We will investigate the
contribution of Mef2c to brown adipogenesis and metabolic function using cells and mice in which Mef2c has
been deleted. For specific aim 3, we will determine the physiological contribution of scBAT to energy and
glucose homeostasis in vivo by investigating the effects of loss of scBAT in healthy mice and the underlying
mechanism of action by which scBAT regulates metabolism. We will also determine whether loss of scBAT
further disrupts metabolic function in high-fat diet induced obese mice. Together these studies should provide
fundamental understanding of the origin of, the contribution of Mef2c to the function of, and physiological
significance of scBAT in mice and provide new insight into how to potentially utilize the most common active
BAT depot in humans to treat obesity and its related metabolic complications.

## Key facts

- **NIH application ID:** 9851860
- **Project number:** 5R01DK116899-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Miaohsueh Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $350,000
- **Award type:** 5
- **Project period:** 2019-01-18 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851860

## Citation

> US National Institutes of Health, RePORTER application 9851860, Genetic and Functional Investigation of Supraclavicular Brown Adipose Tissue (5R01DK116899-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9851860. Licensed CC0.

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