# Deconstructing the brown neogenic zone in classic brown adipose tissue

> **NIH NIH F31** · WAYNE STATE UNIVERSITY · 2020 · $34,814

## Abstract

Project Summary/Abstract
 Global incidence of Type 2 Diabetes (T2D) has reached epidemic proportions, and increasing evidence
indicates that dysfunctional adipose tissue is an important contributor to the pathogenesis of T2D. Expanding
catabolic adipocyte phenotypes within adipose tissues through adrenergic activation improves energy balance
and insulin sensitivity. In order to exploit this remodeling of adipose tissue for therapeutic benefit, we need to
understand the mechanisms by which adrenergic signaling expand the population of catabolic adipocytes in
vivo.
 Brown adipose tissue (BAT) is a thermogenic organ and experimental activation of BAT in rodents
improves metabolic profiles in models of T2D. BAT is also present in adult humans, where cold-induced activity
is correlated with metabolic health. However, the amount of human BAT is highly variable and has low
thermogenic activity. Therefore, in order to expand the thermogenic activity of BAT in humans, it is necessary
to understand the source of new brown adipocytes and how they are recruited and maintained in adult
mammals.
 BAT neogenesis is the principal means by which cold exposure expands thermogenic capacity, and
thus cold-induced neogenesis provides a physiologically relevant model of brown adipogenesis in vivo.
Previous work from our lab has demonstrated that brown adipogenesis occurs within a spatially defined tissue
zone and involves the proliferation of adipocytes progenitors, tissue monocytes/macrophages, capillary
endothelial cells, as well as an uncharacterized population of stromal cells. The overall goal of this proposal
is to deconstruct the neogenic zone in adult BAT, and to test specific mechanisms by which
adrenergic signaling induces BAT neogenesis.
 We proposed to use single cell RNA-sequencing (scRNA-seq) to deconstruct the cell types present in
the brown neogenic zone in a comprehensive and unbiased fashion. Single cell profiling over the course of
cold-induced neogenesis will define the cell types involved, and identify the differentiation trajectories of
activated brown adipocyte progenitors in vivo. In addition, we will address specific mechanisms by which
neural activation triggers tissue expansion using novel genetic loss-of-function analyses.
 The project will not only significantly advanced our understanding of the composition of brown adipose
tissue and how beta adrenergic receptor activation leads to neogenesis in vivo, but will introduce new and
innovative tools to the field, such as smFISH and scRNA-seq. The team of mentors, having highly
complementary expertise, will provide an integrative, multidisciplinary training experience.

## Key facts

- **NIH application ID:** 9889114
- **Project number:** 5F31DK116536-03
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Rayanne Burl
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $34,814
- **Award type:** 5
- **Project period:** 2018-03-26 → 2021-03-25

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889114

## Citation

> US National Institutes of Health, RePORTER application 9889114, Deconstructing the brown neogenic zone in classic brown adipose tissue (5F31DK116536-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9889114. Licensed CC0.

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