# Cellular mechanobiology and engineering of active brown adipose tissue

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $570,908

## Abstract

PROJECT SUMMARY/ABSTRACT
There is a dire need for new technologies to address the obesity epidemic and its associated sequellae,
including Type II Diabetes. Increasing caloric output through expansion and activation of brown adipose tissue
(BAT), which “burns” metabolic fuels to produce heat, is garnering increasing interest as a novel mechanism to
trigger weight loss in adults. However, the technological translation of this approach, including the engineering
of biomaterial platforms to support BAT in vitro and in vivo, has been limited by a poor understanding of how
cues from the physical microenvironment regulate BAT activation. Our preliminary data hint at a novel and
unexpected model in which beta-adrenergic (ß-AR) stimulation triggers BAT activation through a myosin- and
YAP/TAZ-dependent mechanotransductive signaling network, ultimately enhancing expression of the heat-
generating mitochondrial protein UCP1. This model has profound implications, because it would suggest
that incorporation of mechanical cues within the microenvironment could be leveraged to activate BAT
and promote caloric output as a strategy to combat obesity. Thus, the goal of this proposal is to critically
test the hypothesis that ß-AR and mechanotransductive signaling collude to stimulate BAT activation and
enhanced cellular respiration. We have three aims: (1) To dissect the mechanisms through which actomyosin
tension acutely activates BAT; (2) To determine how mechanical activation of YAP/TAZ regulates expression
of UCP1; and (3) To investigate the role of mechanosensitive YAP/TAZ-dependent signals in white/beige
adipose fate determination. In addition to detailed dissection of signaling events, our approach features an
innovative combination of engineered materials, mechanical stimulation, advanced mouse genetic models,
inducible expression of myosin-activating proteins, and measurements of cell and tissue mechanics.
Successful completion of this work would substantially advance our mechanistic understanding of BAT
activation while informing the design of materials technologies to stimulate BAT activation to reduce obesity.

## Key facts

- **NIH application ID:** 9912145
- **Project number:** 5R01DK118940-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Sanjay Kumar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $570,908
- **Award type:** 5
- **Project period:** 2019-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912145

## Citation

> US National Institutes of Health, RePORTER application 9912145, Cellular mechanobiology and engineering of active brown adipose tissue (5R01DK118940-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9912145. Licensed CC0.

---

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