# The role of vascular endothelium in BAT expansion and remodeling

> **NIH NIH K01** · NEW YORK UNIVERSITY · 2021 · $108,765

## Abstract

Project Summary/Abstract
The rising prevalence of obesity and its comorbidities is a major global health concern. The development of
strategies to prevent or treat human obesity is therefore of the utmost importance. Brown adipose tissue (BAT)
and its related beige fat are specialized for energy expenditure. The identification of metabolically active brown
and beige fat in adult humans has positioned this tissue at the center of investigations into human energy
metabolism. Considering the formidable capacity of BAT for energy expenditure and its role in fatty acid and
glucose metabolism, strategies leading to increased mass or enhanced activity of BAT can potentially be utilized
to combat obesity and its related metabolic disorders. Different adipose depots undergo massive remodeling in
response to environmental stimuli, such as cold and diet. Prolonged cold exposure leads to recruitment of new
brown adipocytes as well as a coordinated expansion and remodeling of vascular endothelium in classical BAT
to enable maximal thermogenic capacity. However, the cellular origin of the cold-induced brown adipocytes, and
the identity of intracellular communication pathways coordinating the adipogenesis and angiogenesis are not
known. The overall goal of this proposal is to identify the role of endothelial cells in BAT expansion and
remodeling in response to cold exposure and high fat diet. To address this, we used single cell RNA-sequencing
(scRNA-seq) to uncover the temperature-dependent remodeling of each cell type within BAT. The preliminary
data have made the novel discovery that cold exposure triggers the induction of brown adipocyte thermogenic
program in endothelial cells (ECs). Additionally, the cell-type specific gene expression data allowed the
identification of a Slit3-Robo4 as a potential ligand-receptor interaction mediating the crosstalk between
adipocyte progenitors and ECs. The central hypotheses are that ECs contribute to cold-induced BAT expansion
through de novo differentiation to thermogenic adipocytes and that Slit3 secretion from adipocyte progenitors
promotes EC proliferation and angiogenesis through interaction with EC Robo4 receptor. This proposal will
determine the contribution of ECs to thermogenic adipocytes pool (Aim 1) and will address the role of Slit3-
Robo4 interaction in regulating adipose tissue remodeling and angiogenesis in response to high fat feeding (Aim
2). Successful completion of this proposal will change the current premise and will establish novel molecular
players linking adipogenesis and angiogenesis and will have profound biomedical implications. The mentored
career development award will be used to achieve a series of training objectives including expanding applicant’s
knowledge in vascular biology and professional development skills that are essential for transition to an
independent investigator. The training plan will build upon applicant’s expertise in adipose tissue biology and will
enable the establishme...

## Key facts

- **NIH application ID:** 10487708
- **Project number:** 7K01DK125608-03
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Farnaz Shamsi
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $108,765
- **Award type:** 7
- **Project period:** 2020-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10487708

## Citation

> US National Institutes of Health, RePORTER application 10487708, The role of vascular endothelium in BAT expansion and remodeling (7K01DK125608-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10487708. Licensed CC0.

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