# Integrating cellular metabolic pathways into browning of white fat

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $434,700

## Abstract

SUMMARY
Browning of white adipose tissue is increasingly recognized as a potential new therapeutic target for the
treatment of obesity and diabetes. The mechanisms that govern this process remain incompletely understood,
in particular how the process is linked to intracellular metabolic cues. We have now uncovered a novel
molecular pathway that regulates browning of white fat, and which integrates two of the most important
intracellular metabolic sensors: mTOR and AMPK. At the heart of this pathway lies Folliculin (FLCN), a protein
mutated in the hamartomatous Birt-Hogg-Dube syndrome. FLCN interacts directly with, and transduces
signals, to and from both the mTOR and AMPK pathways. The absence of FLCN in adipose tissue leads to
marked browning of white fat, and dramatic potentiation of thermogenesis. We thus hypothesize that FLCN in
white adipose tissue is a key nexus that integrates metabolic cues to coordinate the browning of white
fat. We propose experiments to:
 1) Delineate the molecular mechanisms by which FLCN, mTOR, and AMPK regulate browning in fat.
 2) Use genetic epistatic experiments in intact mice to definitively test the role of this novel axis in browning
 of fat in vivo.
 3) Test if inhibition of adipocyte FLCN improves metabolic homeostasis and can protect from obesity and
 diabetes in both diet-induced and genetic murine models.

## Key facts

- **NIH application ID:** 9965657
- **Project number:** 5R01DK107667-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Zoltan P Arany
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $434,700
- **Award type:** 5
- **Project period:** 2016-07-15 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965657

## Citation

> US National Institutes of Health, RePORTER application 9965657, Integrating cellular metabolic pathways into browning of white fat (5R01DK107667-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9965657. Licensed CC0.

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