Inhibition of Soluble Epoxide Hydrolase Is Protective against the Multiomic Effects of a High Glycemic Diet on Brain Microvascular Inflammation and Cognitive Dysfunction

Diet is a modifiable risk factor for cardiovascular disease (CVD) and dementia, yet relatively little is known about the effect of a high glycemic diet (HGD) on the brain’s microvasculature. The objective of our study was to determine the molecular effects of an HGD on hippocampal microvessels and c...

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Autores principales:	Saivageethi Nuthikattu, Dragan Milenkovic, Jennifer E. Norman, John Rutledge, Amparo Villablanca
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	multi-omics microvascular brain dementia high glycemic diet soluble epoxide hydrolase inhibitor Nutrition. Foods and food supply TX341-641
Acceso en línea:	https://doaj.org/article/00952db948ed4ebfa16ad87f53db19c6
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spelling	oai:doaj.org-article:00952db948ed4ebfa16ad87f53db19c62021-11-25T18:35:13ZInhibition of Soluble Epoxide Hydrolase Is Protective against the Multiomic Effects of a High Glycemic Diet on Brain Microvascular Inflammation and Cognitive Dysfunction10.3390/nu131139132072-6643https://doaj.org/article/00952db948ed4ebfa16ad87f53db19c62021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6643/13/11/3913https://doaj.org/toc/2072-6643Diet is a modifiable risk factor for cardiovascular disease (CVD) and dementia, yet relatively little is known about the effect of a high glycemic diet (HGD) on the brain’s microvasculature. The objective of our study was to determine the molecular effects of an HGD on hippocampal microvessels and cognitive function and determine if a soluble epoxide hydrolase (sEH) inhibitor (sEHI), known to be vasculoprotective and anti-inflammatory, modulates these effects. Wild type male mice were fed a low glycemic diet (LGD, 12% sucrose/weight) or an HGD (34% sucrose/weight) with/without the sEHI, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), for 12 weeks. Brain hippocampal microvascular gene expression was assessed by microarray and data analyzed using a multi-omic approach for differential expression of protein and non-protein-coding genes, gene networks, functional pathways, and transcription factors. Global hippocampal microvascular gene expression was fundamentally different for mice fed the HGD vs. the LGD. The HGD response was characterized by differential expression of 608 genes involved in cell signaling, neurodegeneration, metabolism, and cell adhesion/inflammation/oxidation effects reversible by t-AUCB and hence sEH inhibitor correlated with protection against Alzheimer’s dementia. Ours is the first study to demonstrate that high dietary glycemia contributes to brain hippocampal microvascular inflammation through sEH.Saivageethi NuthikattuDragan MilenkovicJennifer E. NormanJohn RutledgeAmparo VillablancaMDPI AGarticlemulti-omicsmicrovascularbraindementiahigh glycemic dietsoluble epoxide hydrolase inhibitorNutrition. Foods and food supplyTX341-641ENNutrients, Vol 13, Iss 3913, p 3913 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	multi-omics microvascular brain dementia high glycemic diet soluble epoxide hydrolase inhibitor Nutrition. Foods and food supply TX341-641
spellingShingle	multi-omics microvascular brain dementia high glycemic diet soluble epoxide hydrolase inhibitor Nutrition. Foods and food supply TX341-641 Saivageethi Nuthikattu Dragan Milenkovic Jennifer E. Norman John Rutledge Amparo Villablanca Inhibition of Soluble Epoxide Hydrolase Is Protective against the Multiomic Effects of a High Glycemic Diet on Brain Microvascular Inflammation and Cognitive Dysfunction
description	Diet is a modifiable risk factor for cardiovascular disease (CVD) and dementia, yet relatively little is known about the effect of a high glycemic diet (HGD) on the brain’s microvasculature. The objective of our study was to determine the molecular effects of an HGD on hippocampal microvessels and cognitive function and determine if a soluble epoxide hydrolase (sEH) inhibitor (sEHI), known to be vasculoprotective and anti-inflammatory, modulates these effects. Wild type male mice were fed a low glycemic diet (LGD, 12% sucrose/weight) or an HGD (34% sucrose/weight) with/without the sEHI, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), for 12 weeks. Brain hippocampal microvascular gene expression was assessed by microarray and data analyzed using a multi-omic approach for differential expression of protein and non-protein-coding genes, gene networks, functional pathways, and transcription factors. Global hippocampal microvascular gene expression was fundamentally different for mice fed the HGD vs. the LGD. The HGD response was characterized by differential expression of 608 genes involved in cell signaling, neurodegeneration, metabolism, and cell adhesion/inflammation/oxidation effects reversible by t-AUCB and hence sEH inhibitor correlated with protection against Alzheimer’s dementia. Ours is the first study to demonstrate that high dietary glycemia contributes to brain hippocampal microvascular inflammation through sEH.
format	article
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
title	Inhibition of Soluble Epoxide Hydrolase Is Protective against the Multiomic Effects of a High Glycemic Diet on Brain Microvascular Inflammation and Cognitive Dysfunction
title_short	Inhibition of Soluble Epoxide Hydrolase Is Protective against the Multiomic Effects of a High Glycemic Diet on Brain Microvascular Inflammation and Cognitive Dysfunction
title_full	Inhibition of Soluble Epoxide Hydrolase Is Protective against the Multiomic Effects of a High Glycemic Diet on Brain Microvascular Inflammation and Cognitive Dysfunction
title_fullStr	Inhibition of Soluble Epoxide Hydrolase Is Protective against the Multiomic Effects of a High Glycemic Diet on Brain Microvascular Inflammation and Cognitive Dysfunction
title_full_unstemmed	Inhibition of Soluble Epoxide Hydrolase Is Protective against the Multiomic Effects of a High Glycemic Diet on Brain Microvascular Inflammation and Cognitive Dysfunction
title_sort	inhibition of soluble epoxide hydrolase is protective against the multiomic effects of a high glycemic diet on brain microvascular inflammation and cognitive dysfunction
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/00952db948ed4ebfa16ad87f53db19c6
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Inhibition of Soluble Epoxide Hydrolase Is Protective against the Multiomic Effects of a High Glycemic Diet on Brain Microvascular Inflammation and Cognitive Dysfunction

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