# Developmental and Dynamic Regulation of the Crosstalk between Adipocytes and the Sympathetic Nervous System

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2020 · $466,572

## Abstract

Obesity affects more than one in three adults in the United States and contributes to the leading causes of
morbidity and mortality. Addressing this public health emergency will require new approaches supported by
deeper understanding of fundamental biological mechanisms. Fat cells or adipocytes have been a focus of
basic research into obesity and metabolic disease. Mammals possess white adipocytes that are efficient at
storing energy and thermogenic brown and beige adipocytes that can convert energy into heat. The activation
of beige fat cells is associated with anti-obesity and anti-diabetes effects. Beige fat cell function is dependent
on the transcriptional coregulatory protein PRDM16. While the molecular pathways governing beige adipocyte
development and phenotype have been increasingly delineated, little is known about how beige adipocytes
interact with other cell types within adipose tissue. We developed a novel three-dimensional whole tissue
imaging technique to provide insights into cellular crosstalk within adipose tissue. We discovered a regional
preference for beige fat biogenesis and a regulated interaction between beige adipocytes and the sympathetic
nervous system (SNS). Employing mouse models with adipocyte-specific Prdm16 loss of function, we found
that PRDM16 in adipocytes regulates sympathetic neurite projections to these cells. Here we propose to
address two aims to elucidate the mechanisms underlying the crosstalk between beige adipocytes and the
SNS. First, we will investigate whether sympathetic projections to adipose tissue are established during
development and/or show plasticity in different physiological contexts. Second, we will test the role of several
candidate pathways in modulating the communication between beige adipocytes and sympathetic neurons. In
addition, we will employ a cell-type selective proteomic approach to comprehensively characterize the
molecular components involved in the interaction between beige adipocytes and sympathetic projections. This
proposal will provide an integrated view of adipose tissue, including its architecture and the interaction between
beige adipocytes and projections from the sympathetic nervous system. These studies will produce important
technical and conceptual advances that address knowledge gaps in our understanding of adipose tissue
biology and will yield new mechanism-based therapeutic targets for the treatment of obesity and associated
diseases.

## Key facts

- **NIH application ID:** 9903294
- **Project number:** 5R01DK120649-02
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Paul Cohen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $466,572
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9903294

## Citation

> US National Institutes of Health, RePORTER application 9903294, Developmental and Dynamic Regulation of the Crosstalk between Adipocytes and the Sympathetic Nervous System (5R01DK120649-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9903294. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*