# Central mechanisms of fibroblast growth factor-21 to decrease hepatic triglycerides

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $38,440

## Abstract

PROJECT SUMMARY
 Non-alcoholic fatty liver disease (NAFLD) is a co-morbidity of obesity that is increasing in prevalence
and now affects a quarter of the global population. Critically, there are currently no available therapeutics for
NAFLD, making the need for a novel therapeutic that decreases hepatic triglycerides increasingly urgent.
Fibroblast growth factor-21 (FGF21) is a liver-produced hormone that consistently decreases hepatic
triglycerides when given pharmacologically and thus has gained tremendous interest as a potential therapeutic
for NAFLD. Consequently, several pharmaceutical companies are actively developing FGF21-analogs. Indeed,
a recent and exciting clinical trial found promising results of an FGF21-analog to ameliorate NAFLD. However,
the mechanisms by which FGF21 decreases hepatic triglycerides is unclear. This presents a major obstacle in
discovering new potential targets for the treatment of NAFLD, which remains exceedingly important. In light of
recent evidence that FGF21 does not act directly on hepatocytes (or adipocytes, an important regulator of
whole-body lipid metabolism) to decrease liver triglycerides, our overarching hypothesis is that FGF21 acts on
the brain to decrease hepatic triglycerides via increased sympathetic drive to the liver. We will test this
hypothesis by determining the sufficiency (Aim 1) and necessity (Aim 2) of FGF21 action in the brain to
decrease hepatic triglycerides via increased sympathetic drive to the liver. Additionally, our preliminary data
suggest that FGF21 acts in the suprachiasmatic nucleus (SCN) of the hypothalamus; thus, we will test the
importance of this brain region to mediate FGF21’s hepatic effects. We will test these hypotheses using
techniques including intracerebroventricular and intra-SCN cannulation, genetic knockdown models, site-
specific stereotactic delivery of AAVs, and hepatic sympathectomy. Successful completion of these
experiments will not only further our understanding of FGF21 and the role of the brain to regulate hepatic lipid
metabolism, but will also provide new insights into potential targets for the treatment of NAFLD. Importantly, in
addition to the experiments outlined in the Research Strategy, the present proposal includes wholistic training
for scientific and professional development. This training will be facilitated by intentional mentorship by the
sponsor and co-sponsor, professional development activities, and the outstanding facilities and expertise
available at UC Davis. Together, the present proposal will aid in my preparation for my next career stage and
advance me toward my long-term goal of becoming an academic scientist conducting translational research in
the field of metabolism.

## Key facts

- **NIH application ID:** 10124985
- **Project number:** 5F31DK124080-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Aki Terata-Bowers Chaffin
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,440
- **Award type:** 5
- **Project period:** 2020-03-26 → 2022-03-25

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10124985

## Citation

> US National Institutes of Health, RePORTER application 10124985, Central mechanisms of fibroblast growth factor-21 to decrease hepatic triglycerides (5F31DK124080-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10124985. Licensed CC0.

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