# HuR as a Regulator of Skeletal Muscle Metabolism

> **NIH NIH K01** · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · 2022 · $112,536

## Abstract

PROJECT SUMMARY/ABSTRACT
The ability to switch between metabolic substrates based on their availability, metabolic flexibility, requires a
complex network of molecular interactions for efficient function. We have found that one aspect of this network
is the control of mRNA transcript levels by HuR. HuR is an RNA-binding protein that regulates levels of RNA
transcripts and their translation within cells. Though HuR has been extensively studied for its roles in
proliferation, inflammation, and apoptosis, its action as a metabolic sensor is relatively unknown. Our
preliminary data indicate that skeletal muscle specific HuR knockout mice show increased insulin resistance
and adiposity relative to control animals. Interestingly, these mice show increased levels of HuR target
transcripts, while also showing decreased translated protein levels for these transcripts. The poor metabolic
prognosis resulting from down regulation of HuR in skeletal muscle also complements data we have collected
for metabolically unhealthy male and female human skeletal muscle samples. The proposed aims will
therefore test the hypothesis that delivery of HuR target transcripts to the ribosome promotes metabolic
flexibility by influencing the mTOR signaling pathway.
Very important is the new methodological techniques that Dr. Warfel will learn in order to develop his career as
an independent investigator focused on RNA biology and metabolism. Methods in this proposal include
transgenic mouse model generation and phenotyping, use of metabolic chambers and radioactive metabolite
assays, bioinformatics and molecular biology. The training in these techniques will also provide the preliminary
data necessary to develop future projects aimed at understanding the contribution of RNA binding proteins to
cellular metabolic homeostasis, and to consider new potential avenues in the treatment of insulin resistance
and obesity. This is Dr. Warfel’s long-term research expectation, and he has assembled an outstanding team
of mentors and collaborators with extensive experience in areas relevant to this proposal who will provide
guidance to ensure that Dr. Warfel achieves independence.

## Key facts

- **NIH application ID:** 10428519
- **Project number:** 5K01DK116914-04
- **Recipient organization:** LSU PENNINGTON BIOMEDICAL RESEARCH CTR
- **Principal Investigator:** Jaycob Dalton Warfel
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $112,536
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10428519

## Citation

> US National Institutes of Health, RePORTER application 10428519, HuR as a Regulator of Skeletal Muscle Metabolism (5K01DK116914-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10428519. Licensed CC0.

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