# Ethanol Regulation of Adiponectin and its Signaling

> **NIH NIH R01** · NORTHEAST OHIO MEDICAL UNIVERSITY · 2020 · $351,000

## Abstract

Alcoholic steatohepatitis is the initial stage of alcoholic liver disease (ALD) and a major risk factor for
advanced liver injuries, including fibrosis/cirrhosis, hepatocellular carcinoma and liver failure. Despite a large
body of evidence suggesting that the early stage of ALD, alcoholic steatohepatitis, is driven by organ crosstalk,
lack of knowledge on the inter-organ crosstalk endocrine coordinators and their roles in alcoholic steatohepatitis
has hampered the progress of ALD research. This proposal is a competing continuation of the grant, titled
“Ethanol Regulation of Adiponectin and It's Signaling". Our group has recently investigated the underlying
mechanisms of ethanol-mediated impairment of adiponectin signaling by identifying a new target of ethanol
action, fibroblast growth factor (FGF) 15 (human homolog, FGF19), an ileum-derived hormone. We have found
that dysregulated adiponectin-FGF15/19 axis and impaired adiponectin-FGF15/19 signaling are associated with
alcoholic steatohepatitis in rodents and humans. More importantly, adiponectin-FGF15/19 axis confers
protection against ethanol-induced liver damage via fine-tuning the adipose-intestine-liver crosstalk. Therefore,
this current renewal proposal will examine a novel and exciting central hypothesis that adiponectin-FGF15/19
axis plays a pivotal role in the development of alcoholic steatohepatitis. This central hypothesis will be pursued
through three complementary aims. In Aim 1, we will investigate the role of adiponectin-FGF15/19 axis in the
development of alcoholic steatohepatitis in mice. In Aim 2, we will dissect the mechanisms through which ethanol
impairs adiponectin-FGF15/19 signaling in cultured hepatocytes and in mouse livers. In Aim 3, we will investigate
the underlying mechanisms by which ethanol down-regulates FGF15/19 in cultured intestinal cells and in mouse
ileum. We will utilize molecular, cellular, and biochemical approaches with cell culture and in genetically or
adenoviral modified mouse models to dissect the molecular and cellular events mediating the effects of ethanol
on adiponectin-FGF15/19 axis and it's signaling. Pharmacological or nutritional reagents designed to enhancing
or optimizing the adiponectin-FGF15/19 axis may serve novel therapeutic strategies in the management and
treatment of human alcoholic steatohepatitis.

## Key facts

- **NIH application ID:** 9984919
- **Project number:** 5R01AA015951-15
- **Recipient organization:** NORTHEAST OHIO MEDICAL UNIVERSITY
- **Principal Investigator:** Jessica Marie Ferrell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $351,000
- **Award type:** 5
- **Project period:** 2006-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984919

## Citation

> US National Institutes of Health, RePORTER application 9984919, Ethanol Regulation of Adiponectin and its Signaling (5R01AA015951-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984919. Licensed CC0.

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