# Lipotoxicity and Maintenance of Metabolic Health

> **NIH NIH R01** · JOSLIN DIABETES CENTER · 2024 · $573,863

## Abstract

ABSTRACT
Lipotoxicity is an important mechanism of complications in type 2 diabetes, including non-alcoholic fatty liver
disease (NAFLD). Through a genetic screen, we discovered that loss of small nucleolar RNAs (snoRNAs)
embedded within introns of the ribosomal protein L13a (Rpl13a) locus confers resistance to lipotoxicity in a cell
culture model. The four Rpl13a snoRNAs, SNORD32A, SNORD33, SNORD34, and SNORD35A, guide 2¢-O-
methyl nucleotide modifications at five sites on nascent 18S and 28S ribosomal RNAs that lie in close proximity
to key functional centers of the ribosome structure. This study will test the hypothesis that knockout of Rpl13a
snoRNAs protects from lipotoxic tissue damage in a mouse model of high fat diet-induced NAFLD. We will define
the mechanistic links among snoRNA abundance, mRNA translation, and dietary nutrient exposures. Findings
from this work will provide new insights into the pathophysiology of NAFLD and other diseases of lipid overload
and have the potential to identify new therapeutic targets for treatment of metabolic diseases.

## Key facts

- **NIH application ID:** 10873823
- **Project number:** 5R01DK137511-02
- **Recipient organization:** JOSLIN DIABETES CENTER
- **Principal Investigator:** JEAN E. SCHAFFER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $573,863
- **Award type:** 5
- **Project period:** 2023-07-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873823

## Citation

> US National Institutes of Health, RePORTER application 10873823, Lipotoxicity and Maintenance of Metabolic Health (5R01DK137511-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10873823. Licensed CC0.

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