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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| Language: | English |
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The University of Toledo
2025-02-01
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| 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 |
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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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| format | Article |
| id | doaj-art-b17fbaf478cf4d8a90ee8b0bcffb8992 |
| institution | Kabale University |
| issn | 2469-6706 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | The University of Toledo |
| record_format | Article |
| series | Translation |
| 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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