# Integrating LncRNA to Methionine Metabolism in Alcoholic Fatty Liver

> **NIH NIH K01** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $161,379

## Abstract

Abstract
Alcoholic liver disease (ALD) is one of the primary causes of morbidity and mortality in the United States,
which ranges from alcoholic fatty liver (AFL), cirrhosis, to hepatocellular carcinoma. AFL is characterized
by accumulation of lipid in hepatocytes, which represents the initial stage of ALD. Chronic alcohol
consumption can cause abnormal homocysteine (Hcy) and methionine (Met) metabolism, which in turn
contributes to the development and progression of AFL. LncRNA H19 is paternally imprinted lncRNA, and
is highly expressed in fetal liver but diminishes in adult liver. Of particular interest, such expression is
reactivated in human chronic liver disease, implicating an important regulatory role in hepatic function and
metabolism. Our preliminary results demonstrated that hepatic overexpression of H19 promoted alcohol
induced liver injury and steatosis, which was associated with altered hepatic TG profiling and methionine
levels, as revealed by lipidomics and metabolomics analyses. However, the physiological and molecular
action of H19 in AFL remains largely unexplored and warrants further investigation. The overall objective is
to elucidate the mechanistic function of H19 in alcoholic fatty liver. The central hypothesis is that H19
interacts with RNA binding protein polypyrimidine tract-binding protein (PTBP1) to inhibit bataine-
homocysteine S-methltransferase (BHMT) expression and function, which disrupts homocysteine and
methionine metabolism, leading to alcoholic fatty liver. We propose two specific aims to test the central
hypothesis. Aim #1: To characterize the physiological role of H19 in alcoholic fatty liver. Aim #2: To
elucidate the molecular mechanisms by which H19 induces alcoholic fatty liver. The proposed studies build
on our long-standing experiences in studying liver metabolism and disease. We propose to use combined
approaches of molecular biology, systems biology, genome wide high throughput and metabolomics
analysis to investigate the novel regulatory role of IncRNA H19 in AFL. Therefore, the proposed study
would be a pioneering investigation in integrating lncRNA function with methionine metabolism in AFL,
providing advanced understanding of the pathophysiology of AFL.

## Key facts

- **NIH application ID:** 9998806
- **Project number:** 5K01AA026385-03
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Zhihong Yang
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $161,379
- **Award type:** 5
- **Project period:** 2018-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998806

## Citation

> US National Institutes of Health, RePORTER application 9998806, Integrating LncRNA to Methionine Metabolism in Alcoholic Fatty Liver (5K01AA026385-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9998806. Licensed CC0.

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