# Regulation of Liver Metabolism by lncRNAs

> **NIH NIH R03** · UNIVERSITY OF PENNSYLVANIA · 2020 · $77,280

## Abstract

Project Summary
The current research proposal is to investigate the physiological function of Gm11967, a novel insulin-dependent
long non-coding RNA (lncRNA) identified during my current K01 award. Despite ncRNAs accounting for a
majority of the transcriptome, very little is known about their biological significance and functional targets.
lncRNAs are a large and diverse class of RNA transcripts with a length of more than 200 nucleotides that do not
encode proteins. To date, very few lncRNAs have been characterized in detail; however, recent work has
suggested a potential role for lncRNA in metabolic disorders such as diabetes and obesity. Therefore, we re-
analyzed genome-wide data sets generated during my K01 award to interrogate the role of hepatic insulin
signaling on lncRNA expression to identify novel, metabolically regulated lncRNAs. We identified Gm11967 as
one of the most significantly induced lncRNA in liver in vivo. Using mouse genetics, we demonstrated Gm11967
is downstream of the Akt-Foxo1 axis, a central signaling node involved in hepatic glucose and lipid metabolism.
Gm11967 shares a transcription start site with glucokinase, a potent insulin-regulated gene that is the focus of
my current K01. Given its robust activation with feeding, dependency on insulin action, and close association
with glucokinase expression, we hypothesized that Gm11967 plays a central role in the regulation of hepatic
glucose and lipid metabolism. We will perform gain and loss of function experiments in vivo to elucidate the
biological function of Gm11967 in hepatocytes. In addition, we will perform chromatin isolation by RNA
purification (ChIRP) followed by mass spectrometry and/or deep sequencing to identify functional proteomic and
genomic targets of Gm11967. Based on my training and expertise obtained during the course of my K01, I have
the independence and technical skillsets necessary to complete this proposal. Importantly, these data will build
upon the strong foundation of my K01 and will enable new lines of investigation that will lead to a future R01
application.

## Key facts

- **NIH application ID:** 9975166
- **Project number:** 5R03DK122191-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Paul Michael Titchenell
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $77,280
- **Award type:** 5
- **Project period:** 2019-07-09 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975166

## Citation

> US National Institutes of Health, RePORTER application 9975166, Regulation of Liver Metabolism by lncRNAs (5R03DK122191-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9975166. Licensed CC0.

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