# The Role of Ceramides in Skeletal Muscle

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $645,781

## Abstract

SUMMARY
Overnutrition and physical inactivity promote the accumulation of sphingolipids such as ceramides which block
insulin signaling and anabolic metabolism. Implementation of pharmacological or genetic interventions to reduce
sphingolipid levels in rodents prevents or reverses an impressive array of metabolic pathologies (e.g. insulin
resistance, diabetes, steatohepatitis, hypertension, cardiomyopathy, and atherosclerosis). To elucidate the
tissue-specific mechanisms through which ceramides contribute to these diseases, we have produced mice
allowing for the conditional, cell-type restricted ablation of enzymes required for ceramide biosynthesis or
degradation (i.e. serine palmitoyltransferase and dihydroceramide desaturases-1) or degradation (i.e. acid
ceramidase). We will apply these tools to dissect the regulatory mechanisms controlling ceramide synthesis and
action in skeletal muscle. Aims of the project include the following:
 To use these novel mouse models to evaluate the effect of muscle-specific ceramide depletion or
 induction on insulin sensitivity, muscle growth, and genomic/proteomic signatures under conditions of
 overnutrition and inactivity.
 To apply a ceramide flux assay in isolated human myotubes to identify the regulatory mechanisms that
 influence rates of ceramide biosynthesis; and,
 To determine the efficacy of a new class of inhibitors of dihydroceramide desaturases-1, our preferred
 target in the ceramide synthesis pathway, as therapeutics that improve muscle insulin sensitivity and
 prevent muscle loss in rodents.
Findings obtained from these studies could uncover new nutrient-sensing machinery that modulates insulin
sensitivity and muscle growth. Moreover, the translational component could lead to new pharmacological
approaches for improving muscle health.

## Key facts

- **NIH application ID:** 10069379
- **Project number:** 5R01DK115824-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** SCOTT A SUMMERS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $645,781
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10069379

## Citation

> US National Institutes of Health, RePORTER application 10069379, The Role of Ceramides in Skeletal Muscle (5R01DK115824-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10069379. Licensed CC0.

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