The effects of the ketone body ?-hydroxybutyrate on the neuronal transcriptome

The ketogenic diet is emerging as an effective therapeutic option for patients with neurological disorders. The diet results in metabolism of fatty acids to ketone bodies like ?-hydroxybutyrates (BHBs), which serve as an alternative fuel source for brain cells. However, the molecular effect of BHB...

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Main Authors: Zayn Cheema, Megan Chen, Dana Poon, Taara Reddy, John Vergis, Sinead O'Donovan
Format: Article
Language:English
Published: The University of Toledo 2025-02-01
Series:Translation
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Online Access:https://openjournals.utoledo.edu/index.php/translation/article/view/1359
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author Zayn Cheema
Megan Chen
Dana Poon
Taara Reddy
John Vergis
Sinead O'Donovan
author_facet Zayn Cheema
Megan Chen
Dana Poon
Taara Reddy
John Vergis
Sinead O'Donovan
author_sort Zayn Cheema
collection DOAJ
description The ketogenic diet is emerging as an effective therapeutic option for patients with neurological disorders. The diet results in metabolism of fatty acids to ketone bodies like ?-hydroxybutyrates (BHBs), which serve as an alternative fuel source for brain cells. However, the molecular effect of BHB on neurons is not well understood. We hypothesized that BHB administration will induce upregulation of energy metabolism-related processes in neurons. To assess the effect of BHB administration on the neuronal transcriptome, we reanalyzed a publicly available RNAseq dataset (GSE252513) using a bioinformatic “3-pod” approach. We conducted pathway analysis and identified leading edge genes using Gene Set Enrichment Analysis (GSEA) and conducted chemical perturbagen analysis using the iLINCS repository to identify drugs that are concordant and discordant with BHB administration. We identified significantly altered (p<0.05) pathways associated with inflammation and immunity such as “regulation of proinflammatory cytokine production” and “modulation of inflammatory responses.” We did not identify significant modulation of energy metabolism-related pathways in response to BHB administration. Our results suggest that under normal conditions, BHBs primary actions include modulation of cellular neuronal immune responses.
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spelling doaj-art-b17fbaf478cf4d8a90ee8b0bcffb89922025-02-05T18:17:54ZengThe University of ToledoTranslation2469-67062025-02-0113S110.46570/utjms-2025-1359The effects of the ketone body ?-hydroxybutyrate on the neuronal transcriptome Zayn CheemaMegan ChenDana PoonTaara ReddyJohn VergisSinead O'Donovan0University of Limerick, Ireland The ketogenic diet is emerging as an effective therapeutic option for patients with neurological disorders. The diet results in metabolism of fatty acids to ketone bodies like ?-hydroxybutyrates (BHBs), which serve as an alternative fuel source for brain cells. However, the molecular effect of BHB on neurons is not well understood. We hypothesized that BHB administration will induce upregulation of energy metabolism-related processes in neurons. To assess the effect of BHB administration on the neuronal transcriptome, we reanalyzed a publicly available RNAseq dataset (GSE252513) using a bioinformatic “3-pod” approach. We conducted pathway analysis and identified leading edge genes using Gene Set Enrichment Analysis (GSEA) and conducted chemical perturbagen analysis using the iLINCS repository to identify drugs that are concordant and discordant with BHB administration. We identified significantly altered (p<0.05) pathways associated with inflammation and immunity such as “regulation of proinflammatory cytokine production” and “modulation of inflammatory responses.” We did not identify significant modulation of energy metabolism-related pathways in response to BHB administration. Our results suggest that under normal conditions, BHBs primary actions include modulation of cellular neuronal immune responses. https://openjournals.utoledo.edu/index.php/translation/article/view/1359Neurontranscriptomeketone body
spellingShingle Zayn Cheema
Megan Chen
Dana Poon
Taara Reddy
John Vergis
Sinead O'Donovan
The effects of the ketone body ?-hydroxybutyrate on the neuronal transcriptome
Translation
Neuron
transcriptome
ketone body
title The effects of the ketone body ?-hydroxybutyrate on the neuronal transcriptome
title_full The effects of the ketone body ?-hydroxybutyrate on the neuronal transcriptome
title_fullStr The effects of the ketone body ?-hydroxybutyrate on the neuronal transcriptome
title_full_unstemmed The effects of the ketone body ?-hydroxybutyrate on the neuronal transcriptome
title_short The effects of the ketone body ?-hydroxybutyrate on the neuronal transcriptome
title_sort effects of the ketone body hydroxybutyrate on the neuronal transcriptome
topic Neuron
transcriptome
ketone body
url https://openjournals.utoledo.edu/index.php/translation/article/view/1359
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