# Regulation of Energy Homeostasis by FGF21

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2020 · $524,132

## Abstract

Project Summary / Abstract
Obesity is a major contributor to the epidemic of metabolic diseases including dyslipidemia, cardiovascular
disease, and type II diabetes. Numerous studies suggest that increasing energy expenditure can effectively
decrease body weight. However, no current therapeutic compounds safely or selectively activate energy
expenditure. The endocrine hormone fibroblast growth factor 21 (FGF21) decreases body weight during
obesity by increasing energy expenditure without affecting physical activity. Moreover, FGF21 potently
decreases both fat and body mass in obese animals and human patients. However, the mechanism for
FGF21-mediated increases in energy expenditure has not been identified. Work from our lab and others have
demonstrated that FGF21 acts in the central nervous system to promote weight loss. In addition, several lines
of evidence suggest that FGF21 requires intact signaling from the adipose-derived hormone, leptin, to elicit its
full effects on driving weight loss. Finally, our preliminary data demonstrates that the obligate FGF21 co-
receptor, β-klotho, is expressed in the arcuate nucleus (ARC) and ventromedial hypothalamus (VMH), primary
sites of leptin action in the brain, and that leptin activates signaling in β-klotho-expressing cells in the VMH and
ARC. Thus, we hypothesize that FGF21 signals, at least in part, to leptin-sensitive cells in the VMH and/or
ARC to modulate energy expenditure. This proposal employs novel genetic mouse models, chemogenetic
manipulation of neurons, and pharmacological approaches to investigate the crosstalk between FGF21 and
leptin signaling in the central control of energy homeostasis. Through these studies we aim to identify novel
therapeutic targets for the treatment of obesity and obesity-associated disorders.

## Key facts

- **NIH application ID:** 10118923
- **Project number:** 2R01DK106104-06A1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Matthew Joseph Potthoff
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $524,132
- **Award type:** 2
- **Project period:** 2015-07-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10118923

## Citation

> US National Institutes of Health, RePORTER application 10118923, Regulation of Energy Homeostasis by FGF21 (2R01DK106104-06A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10118923. Licensed CC0.

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