# Ethanolamine Phosphate Phospholyase in Astrocyte Lipid Metabolism

> **NIH NIH F31** · JOHNS HOPKINS UNIVERSITY · 2020 · $39,179

## Abstract

Dietary changes have been shown to affect nervous system function as well as influence animal behavior as
best exhibited by diet-based treatments for neurological disorders. Ketogenic diets are used to treat individuals
suffering from epileptic seizures while caloric restriction is known to influence circadian rhythm, foraging
behavior, and anxiety-like behaviors in rodents. To enact changes in cognition and behavior, transcriptional
programs must exist in the brain that lead to downstream changes in nervous system structure and function in
response to changes in peripheral metabolites. Diet-specific transcriptional programs in the brain, however, are
not well characterized. Ethanolamine phosphate phospholyase (ETNPPL) is a PLP-dependent enzyme
capable of irreversibly degrading the phospholipid precursor ethanolamine phosphate to acetaldehyde,
ammonium, and inorganic phosphate. Etnppl is enriched in mature astrocytes within the central nervous
system. Interestingly, there is an 8-fold increase in relative Etnppl mRNA after an 18-hour fasting period in
hippocampal astrocytes isolated from mice. In humans, Etnppl mRNA is increased 2-fold in brains of
schizophrenics and decreased 72% in depressed individuals. The manner and purpose of this diet-induced
transcriptional control is not known nor are ETNPPL’s implications in neurological diseases. The central
hypothesis of this proposal is that ETNPPL plays a role in regulating metabolic homeostasis within the central
nervous system which may influence nervous system function and structure as well as influence animal
behavior. We will study the contribution of ETNPPL in the nervous system using a constitutive knockout mouse
to address the following specific aims:
Specific Aim I: Characterization of ETNPPL and determination of the mechanism(s) of fasting-regulated
Etnppl expression.
1A. Characterize Etnppl gene and protein expression, subcellular localization, and activity.
1B. Determine the molecular mechanism of fasting transcriptional control on Etnppl expression upon altered
lipid homeostasis
Specific Aim II: Determine the functional role of ETNPPL on murine metabolic physiology in vivo.
2A. Determine the importance of PEtN-degradation on flux of lipid species using Etnppl-/- mice.
2B. Determine the effect of ETNPPL on metabolic profile using steady-state metabolomics
2C. Determine the role(s) of fasting enrichment of Etnppl on the flux of oxidative substrates using Etnppl-/- mice.
 We expect that contributions from this proposal will provide a greater understanding of transcriptional
programs specific to the brain that are regulated by diet.

## Key facts

- **NIH application ID:** 9829597
- **Project number:** 5F31NS102151-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Cory Justin White
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $39,179
- **Award type:** 5
- **Project period:** 2017-12-01 → 2020-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9829597

## Citation

> US National Institutes of Health, RePORTER application 9829597, Ethanolamine Phosphate Phospholyase in Astrocyte Lipid Metabolism (5F31NS102151-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9829597. Licensed CC0.

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