# Molecular control of beige fat heterogeneity

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2022 · $481,250

## Abstract

PROJECT SUMMARY
Emerging evidence illuminates the biological significance of beige fat, an inducible form of thermogenic fat cells,
in the regulation of metabolic health. The best-known stimulus of beige fat biogenesis is cold acclimation and
subsequent activation of the β3-adrenoceptor (β3-AR) signaling pathway; however, recent studies identified a
variety of external stimuli, such as tissue injury and intermittent fasting, that stimulate beige fat biogenesis
through β3-AR independent pathways. Furthermore, our recent study identified a previously uncharacterized
population of beige fat, referred to as glycolytic beige adipocytes (or g-beige fat), whose developmental
regulation and origin are distinct from β3-AR-induced beige fat.
These results lead us to hypothesize that beige fat is composed of developmentally diverse cell populations, and
that each population plays unique biological roles depending on the nature of external cues (e.g., cold vs. tissue
injury). A technical hurdle to test the hypothesis, however, is the lack of genetic tools that enable us to target
particular adipocyte progenitor populations. Thus, we employed single-cell RNA (scRNA) analysis and identified
two distinct adipocyte progenitor cells (APCs) that give rise to cold-induced beige adipocytes (CD81+ APCs) and
g-beige fat from a myogenic lineage (MyoD+ APCs). Accordingly, this proposal aims to test the above hypothesis
by determining the developmental regulation, molecular mechanisms, and biological function of beige adipocytes
stem from CD81+ APCs and MyoD+ APCs. Our contribution in this proposal is to provide a fundamental
understanding as to how heterogeneous beige adipocyte populations are regulated by physiological and
pathological cues, and how they contribute to the regulation of metabolic tissue homeostasis, such as fuel
oxidation, angiogenesis, innervation, tissue fibrosis, and inflammation.

## Key facts

- **NIH application ID:** 10453783
- **Project number:** 5R01DK125281-03
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Shingo Kajimura
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $481,250
- **Award type:** 5
- **Project period:** 2020-07-20 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10453783

## Citation

> US National Institutes of Health, RePORTER application 10453783, Molecular control of beige fat heterogeneity (5R01DK125281-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10453783. Licensed CC0.

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