High Glycemia and Soluble Epoxide Hydrolase in Females: Differential Multiomics in Murine Brain Microvasculature
The effect of a high glycemic diet (HGD) on brain microvasculature is a crucial, yet understudied research topic, especially in females. This study aimed to determine the transcriptomic changes in female brain hippocampal microvasculature induced by a HGD and characterize the response to a soluble e...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/21/13044 |
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| author | Saivageethi Nuthikattu Dragan Milenkovic Jennifer E. Norman John Rutledge Amparo Villablanca |
| author_facet | Saivageethi Nuthikattu Dragan Milenkovic Jennifer E. Norman John Rutledge Amparo Villablanca |
| author_sort | Saivageethi Nuthikattu |
| collection | DOAJ |
| description | The effect of a high glycemic diet (HGD) on brain microvasculature is a crucial, yet understudied research topic, especially in females. This study aimed to determine the transcriptomic changes in female brain hippocampal microvasculature induced by a HGD and characterize the response to a soluble epoxide hydrolase inhibitor (sEHI) as a mechanism for increased epoxyeicosatrienoic acids (EETs) levels shown to be protective in prior models of brain injury. We fed mice a HGD or a low glycemic diet (LGD), with/without the sEHI (t-AUCB), for 12 weeks. Using microarray, we assessed differentially expressed protein-coding and noncoding genes, functional pathways, and transcription factors from laser-captured hippocampal microvessels. We demonstrated for the first time in females that the HGD had an opposite gene expression profile compared to the LGD and differentially expressed 506 genes, primarily downregulated, with functions related to cell signaling, cell adhesion, cellular metabolism, and neurodegenerative diseases. The sEHI modified the transcriptome of female mice consuming the LGD more than the HGD by modulating genes involved in metabolic pathways that synthesize neuroprotective EETs and associated with a higher EETs/dihydroxyeicosatrienoic acids (DHETs) ratio. Our findings have implications for sEHIs as promising therapeutic targets for the microvascular dysfunction that accompanies vascular dementia. |
| first_indexed | 2024-03-09T19:00:55Z |
| format | Article |
| id | doaj.art-b92a5b5f5e59427e989db365ec6336a9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:00:55Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b92a5b5f5e59427e989db365ec6336a92023-11-24T05:01:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211304410.3390/ijms232113044High Glycemia and Soluble Epoxide Hydrolase in Females: Differential Multiomics in Murine Brain MicrovasculatureSaivageethi Nuthikattu0Dragan Milenkovic1Jennifer E. Norman2John Rutledge3Amparo Villablanca4Division of Cardiovascular Medicine, University of California, Davis, CA 95616, USADepartment of Nutrition, University of California, Davis, CA 95616, USADivision of Cardiovascular Medicine, University of California, Davis, CA 95616, USADivision of Cardiovascular Medicine, University of California, Davis, CA 95616, USADivision of Cardiovascular Medicine, University of California, Davis, CA 95616, USAThe effect of a high glycemic diet (HGD) on brain microvasculature is a crucial, yet understudied research topic, especially in females. This study aimed to determine the transcriptomic changes in female brain hippocampal microvasculature induced by a HGD and characterize the response to a soluble epoxide hydrolase inhibitor (sEHI) as a mechanism for increased epoxyeicosatrienoic acids (EETs) levels shown to be protective in prior models of brain injury. We fed mice a HGD or a low glycemic diet (LGD), with/without the sEHI (t-AUCB), for 12 weeks. Using microarray, we assessed differentially expressed protein-coding and noncoding genes, functional pathways, and transcription factors from laser-captured hippocampal microvessels. We demonstrated for the first time in females that the HGD had an opposite gene expression profile compared to the LGD and differentially expressed 506 genes, primarily downregulated, with functions related to cell signaling, cell adhesion, cellular metabolism, and neurodegenerative diseases. The sEHI modified the transcriptome of female mice consuming the LGD more than the HGD by modulating genes involved in metabolic pathways that synthesize neuroprotective EETs and associated with a higher EETs/dihydroxyeicosatrienoic acids (DHETs) ratio. Our findings have implications for sEHIs as promising therapeutic targets for the microvascular dysfunction that accompanies vascular dementia.https://www.mdpi.com/1422-0067/23/21/13044female sexdementiahigh glycemic dietsoluble epoxide hydrolase inhibitorEETsmulti-omics |
| spellingShingle | Saivageethi Nuthikattu Dragan Milenkovic Jennifer E. Norman John Rutledge Amparo Villablanca High Glycemia and Soluble Epoxide Hydrolase in Females: Differential Multiomics in Murine Brain Microvasculature International Journal of Molecular Sciences female sex dementia high glycemic diet soluble epoxide hydrolase inhibitor EETs multi-omics |
| title | High Glycemia and Soluble Epoxide Hydrolase in Females: Differential Multiomics in Murine Brain Microvasculature |
| title_full | High Glycemia and Soluble Epoxide Hydrolase in Females: Differential Multiomics in Murine Brain Microvasculature |
| title_fullStr | High Glycemia and Soluble Epoxide Hydrolase in Females: Differential Multiomics in Murine Brain Microvasculature |
| title_full_unstemmed | High Glycemia and Soluble Epoxide Hydrolase in Females: Differential Multiomics in Murine Brain Microvasculature |
| title_short | High Glycemia and Soluble Epoxide Hydrolase in Females: Differential Multiomics in Murine Brain Microvasculature |
| title_sort | high glycemia and soluble epoxide hydrolase in females differential multiomics in murine brain microvasculature |
| topic | female sex dementia high glycemic diet soluble epoxide hydrolase inhibitor EETs multi-omics |
| url | https://www.mdpi.com/1422-0067/23/21/13044 |
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