# Regulation of arterial phenotype by perivascular adipose tissue in cardiometabolic disease

> **NIH NIH R01** · MAINEHEALTH · 2022 · $570,170

## Abstract

Obesity and metabolic disease are risk factors for cardiovascular diseases, and their increasing prevalence
has led to increased rates of vascular pathology in our population. Adipocytes have functional specificity based
on their molecular phenotype; white adipocytes store energy in the form of lipids (white adipose tissue), and
thermogenic adipocytes burn calories and generate heat (beige and brown adipose tissue). Within the vascular
microenvironment, blood vessels are surrounded by perivascular adipose tissue (PVAT) that impacts vascular
function. In the mouse, PVAT surrounding the thoracic aorta are brown-like, with high levels of thermogenic
markers, and a clear association with vascular reactivity and vascular disease progression. In humans, aortic
PVAT appears similar to human subcutaneous white adipose tissue, with unilocular adipocytes displaying a
lipid storage phenotype. However, we identified thermogenic markers within human aortic PVAT, and
molecular differences are established between human PVAT from healthy versus diseased vasculature. The
ability to increase the proportion of thermogenic versus white adipose tissue in the body has been suggested
to be an anti-obesity therapeutic strategy, and increasing thermogenesis of PVAT is predicted to be protective
against vascular disease. Thus, it is critical to understand molecular determinants of adipocyte thermogenesis
in humans. In collaborative work, we recently defined novel lineages of thermogenic adipocytes that were
functionally tested in mice. These lineages, interestingly, included a smooth muscle cell (SMC) like adipocyte
lineage, which is relevant to PVAT, which is directly adjacent to the vessel wall. We hypothesize that the
smooth muscle cell-like adipocyte lineage in human PVAT contributes directly to the thermogenic adipocyte
lineage in humans, and that the functional activity of this lineage inversely correlates to vascular disease
progression. This is a translational study with the following specific aims: Aim 1. Define the molecular identity
of the adipocyte progenitor cells in human PVAT, and cellular PVAT composition in vascular pathology. We will
perform molecular studies to identify sub-populations of adipocyte progenitors and overall cellular composition
in human PVAT, and identify associations with clinical and physiological measures of health and disease. Aim
2. Identify the mechanisms driving functional capacity thermogenic adipocyte differentiation in human
adipocyte progenitors, and impact on vascular smooth muscle cell physiology. Differentiation capacity will be
tested in the fibroblast progenitor population and the SMC-like progenitor population, and paracrine signaling
from adipocytes will be evaluated using human vascular SMC. Novel pathways identified from molecular
studies will inform studies to determine drivers of thermogenic differentiation. Our results are expected to
identify for the first time molecular signatures of PVAT corresponding to differen...

## Key facts

- **NIH application ID:** 10443027
- **Project number:** 2R01HL141149-05
- **Recipient organization:** MAINEHEALTH
- **Principal Investigator:** Lucy Liaw
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $570,170
- **Award type:** 2
- **Project period:** 2018-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10443027

## Citation

> US National Institutes of Health, RePORTER application 10443027, Regulation of arterial phenotype by perivascular adipose tissue in cardiometabolic disease (2R01HL141149-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10443027. Licensed CC0.

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