# Adipose tissue plasticity in health and disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $599,749

## Abstract

Abstract
The ability of adipose tissue to handle fluctuations in nutrient availability, by dynamically expanding and
contracting, is critical for survival. However, dysregulation of this process can lead to lipodystrophy, obesity
and dysregulated energy homeostasis. Various factors influence adipocyte plasticity, including anatomical
location, neighboring immune cells, the vasculature and the surrounding extracellular matrix (ECM). While
matrix metalloproteinases (MMPs) have been postulated to participate in the remodeling of the ECM, most
attention has focused on the type I collagen-rich stromal/interstitial ECM. However, mature adipocytes are
surrounded by a specialized form of ECM, termed the basement membrane, that mechanically regulates cell
shape. Without modifying basement membrane assembly or remodeling, changes in adipocyte shape and
storage capacity would not be possible. Nevertheless, the role of the basement membrane in regulating fat
metabolism and function are almost uniformly overlooked. This proposal will seek to document the dynamic
changes in MT1-MMP-mediated basement membrane remodeling in both physiological and pathological states
while identifying the regulatory pathways involved in this process. Aim 1 will provide a characterization of
basement membrane remodeling and corresponding alterations in adipose inflammation, glucose/insulin
homeostasis transcriptional events. Aim 2 will elucidate the mechanism underlying MT1-MMP regulation by
exploring its trafficking to the plasma membrane by insulin. Aim 3 will determine the physiological
consequence of impaired adipose plasticity in states of obesity by investigating adipose-specific conditional KO
mice of MT1-MMP. The experiments outlined in this proposal are designed to explore and expand insights into
the role and regulation of the basement membrane in adipose tissue. The work proposed here lays the
groundwork for future studies into how the basement membrane is modified in adipose tissue, and has
potential to help develop therapeutic targets in the fight against obesity.

## Key facts

- **NIH application ID:** 10617185
- **Project number:** 5R01DK122804-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** ALAN R. SALTIEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $599,749
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10617185

## Citation

> US National Institutes of Health, RePORTER application 10617185, Adipose tissue plasticity in health and disease (5R01DK122804-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10617185. Licensed CC0.

---

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