# The impact of bile acid homeostasis on hepatic xenobiotic receptors

> **NIH NIH F31** · RUTGERS, THE STATE UNIV OF N.J. · 2020 · $31,139

## Abstract

PROJECT SUMMARY/ABSTRACT
 Fibroblast growth factor 15 (Fgf15) is the mouse ortholog of human FGF19. FGF15/19 are endocrine
FGFs produced in the distal small bowel that govern whole-body homeostasis through the regulation of bile
acids, hepatic glucose, and lipid metabolism. Recognizing the pleotropic role of FGF15/19 in regulating
hepatobiliary function, pharmaceutical companies have launched research programs testing the therapeutic
potential of FGF19 to treat numerous liver and metabolic diseases. Nonalcoholic steatohepatitis (NASH) is a
disease that has been characterized by the disregulation of many of the metabolic pathways governed by
FGF19. NASH is rapidly becoming a major health issue in the United States as it affects approximately 3-12%
of the population. There are currently no pharmaceutical therapies for NASH patients. NASH is projected to
overtake hepatitis C virus as leading indication of liver transplant in the United States. The bile acid-FXR-
FGF15/19 pathway is being investigated for its potential for use as a therapeutic intervention of NASH, with
FGF19 protein functioning as a prospective treatment. Our preliminary data suggests that FGF19 protein
alters drug-metabolizing enzymes. Alterations to drug-metabolizing enzymes can lead to drug-drug
interactions, in which a perpetrator drug alters the disposition and/or action of a victim drug when taken in
combination. Drug-drug interactions can lead to the loss of efficacy or toxicity in patients, therefore it is
important to properly evaluate the potential of new therapies to alter drug-metabolizing enzymes. The
research aims in this proposal will investigate the potential of FGF15/19 to bring about changes in drug-
metabolizing enzymes. Aim 1 will descriptively characterize the observed variations and delineate the role of
specific xenobiotic receptors. In addition, we will examine whether or not the observed changes in drug-
metabolizing enzymes from our preliminary data affect the rate at which probe substrates are metabolized.
Aim 2 will use in vitro and in vivo methodologies to elucidate the mechanism by which these changes are
induced. Through the completion of the research and training described in this F31 Fellowship, the Principal
Investigator will be trained in basic and translational biomedical research and will be prepared to conduct
independent research, which is in line with the mission and vision of the National Institute of Diabetes and
Digestive and Kidney Diseases.

## Key facts

- **NIH application ID:** 10049962
- **Project number:** 5F31DK122725-02
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Daniel Rizzolo
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,139
- **Award type:** 5
- **Project period:** 2019-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10049962

## Citation

> US National Institutes of Health, RePORTER application 10049962, The impact of bile acid homeostasis on hepatic xenobiotic receptors (5F31DK122725-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10049962. Licensed CC0.

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