Soluble Epoxide Hydrolase-Derived Linoleic Acid Oxylipins in Serum Are Associated with Periventricular White Matter Hyperintensities and Vascular Cognitive Impairment

Yu, Di; Hennebelle, Marie; Sahlas, Demetrios J.; Ramirez, Joel; Gao, Fuqiang; Masellis, Mario; Cogo‐Moreira, Hugo; Swartz, Richard H.; Herrmann, Nathan; Chan, Pak Cheung; Pettersen, Jacqueline A.; Stuss, Donald T.; Black, Sandra E.; Taha, Ameer Y.; Swardfager, Walter

doi:10.1007/s12975-018-0672-5

Cited by 41 publications

(41 citation statements)

References 32 publications

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“…Frozen collections of serum and plasma from studies of neurocognitive disorders, including measures of cognitive function, provide a resource for biomarker discovery in this arena 22 However, opportunistically collected samples rarely contain information regarding fed/fasted states, which can compromise “omics” analyses. Here, we took advantage of data and biospecimens from subjects in the Religious Order Study and Rush Memory and Aging Project (ROS/MAP) 23 , develop a predictive tool for the fasted/non-fasted state discrimination and stratify our biomarker discovery effort by the fasted state.…”

Section: Introductionmentioning

confidence: 99%

Serum metabolomic biomarkers of perceptual speed in cognitively normal and mildly impaired subjects with fasting state stratification

Borkowski

Taha

Pedersen

et al. 2020

Preprint

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Cognitive decline is associated with both normal aging and early pathologies leading to dementia. Here we used quantitative profiling of metabolites involved in the regulation of inflammation, vascular function, neuronal function and energy metabolism, including oxylipins, endocannabinoids, bile acids, and steroid hormones to identify metabolic biomarkers of mild cognitive impairment (MCI). Serum samples (n =210) were obtained from subjects with or without MCI opportunistically collected with incomplete fasting state information. To maximize power and stratify the analysis of metabolite associations with MCI by the fasting state, we developed an algorithm to predict subject fasting state when unknown (n =71). In non-fasted subjects, linoleic acid and palmitoleoyl ethanolamide levels were positively associated with perceptual speed. In fasted subjects, soluble epoxide hydrolase activity and tauro-alpha-muricholic acid levels were negatively associated with perceptual speed. Other cognitive domains showed associations with bile acid metabolism, but only in the non-fasted state. Importantly, this study shows unique associations between serum metabolites and cognitive function in the fasted and non-fasted states and provides a fasting state prediction algorithm based on measurable metabolites.

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Section: Introductionmentioning

confidence: 99%

Serum metabolomic biomarkers of perceptual speed in cognitively normal and mildly impaired subjects with fasting state stratification

Borkowski

Taha

Pedersen

et al. 2020

Preprint

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“…The EpETrEs are generally considered to be beneficial, having have vasodilatory and anti-inflammatory effects which are lost upon conversion to DiHETrEs [30]. Others have demonstrated an increase in DiHETrEs and other diol products of epoxide hydrolases in the serum and brains of individuals with vascular cognitive impairment compared with controls [31,32]. Our data indicated that epoxide 8,9-EpETrE and diol 14,15-DiHETrE levels were higher in the WM group compared to the LFLSM group and fasting group.…”

Section: Discussionmentioning

confidence: 46%

A single meal has the potential to alter brain oxylipin content

Norman

Aung

Otoki

et al. 2020

Prostaglandins, Leukotrienes and Essential Fatty Acids

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Our objective was to determine whether consumption of a single meal has the potential to alter brain oxylipin content. We examined the cerebrum of mice fed a single high-fat/high-sucrose Western meal or a low-fat/lowsucrose control meal, as well as fasted mice. We found no changes in fatty acid composition of cerebrum across the groups. The cerebral oxylipin profile of mice fed a Western meal is distinct from the profile of mice fed a lowfat/low-sucrose meal. Cerebral gene expression of cyclooxygenase 1, cyclooxygenase 2, and epoxide hydrolase 1 were elevated in Western meal-fed mice compared to low-fat/low-sucrose meal-fed mice. Mice that consumed either meal had lower gene expression of cytochrome P450, family 2, subfamily j, polypeptide 12 than fasted mice. Our data in this hypothesis-generating study indicates that the composition of a single meal has the potential to alter brain oxylipins and the gene expression of the enzymes responsible for their production.

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“…Linoleic acid is rstly metabolized to 12,13-EpOME by cytochrome P450 (CYP) epoxygenases, and followed by hydrolysis catalyzed by soluble epoxide hydrolases (sEHs) to form the diols 12,13-diHOME [83]. They have multiple pathological features, such as decreasing post-ischemic cardiac recovery, participating in the vascular cognitive impairment, increasing skeletal muscle fatty acid uptake and impeding immune tolerance in asthma child [31,[84][85][86]. And the 12,13-diHOME produced by sEH hydrolysis of 12,13-EpOME showed stronger cytotoxicity [83,87].…”

Section: Discussionmentioning

confidence: 99%

Preventive Antibiotic Treatment Increases Neonatal Chicks Susceptibility to Salmonella Infection Via Disrupting Gut Microbiota and Linoleic Acid Metabolism

Mei¹,

Ma²,

Zhai³

et al. 2020

Preprint

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Background: Antimicrobial agents have been widely used in animal farms to prevent and treat animal diseases. However, antimicrobial agents may change the bacterial community and increase susceptibility to the pathogenic bacteria infection. Here, we used metagenomic and metabonomic approach to investigate the effects of florfenicol (FFC) pre-treatment on colonization of Salmonella enterica serovar Enteritidis (S. Enteritidis) in intestines of neonatal chicks through analysis of host responses, microbiota and metabolic changes. Results: We observed that FFC pre-treatment significantly increases the level of S. Enteritidis in the cecal contents, spleen and liver and also induces changes to the cecal microbiota and metabolism. Prior to S. Enteritidis infection, FFC significantly reduced the content of Lactobacillus, and significantly affected the linoleic acid metabolism pathway, including significantly reducing the levels of conjugated linoleic acid (CLA), and significantly increasing the abundance of 12,13-EpOME and 12,13-diHOME in cecum. After infection with S. Enteritidis, the abundance of Proteobacteria were significantly increased and the Salmonella-induced intestinal inflammatory responses and intestinal barrier damage were exacerbated. Supplementation with CLA could maintain intestinal integrity, reduce intestinal inflammation, and directly inhibit Salmonella growth to effectively reduce the Salmonella colonization, whereas the 12,13-diHOME through promoting intestinal inflammation and destroying the intestinal barrier function to support the Salmonella infection. Conclusions: Overall, FFC can decrease levels of Lactobacillus and CLA, and elevate cecal 12,13-diHOME concentrations in neonatal chicks and thereby increases susceptibility to Salmonella infection. This study revealed a potential health impact of antibiotics and disturbed gut microbiota and linoleic acid metabolism might be an intestinal health-impairing attribute and may contribute to Salmonella colonization.

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Soluble Epoxide Hydrolase-Derived Linoleic Acid Oxylipins in Serum Are Associated with Periventricular White Matter Hyperintensities and Vascular Cognitive Impairment

Cited by 41 publications

References 32 publications

Serum metabolomic biomarkers of perceptual speed in cognitively normal and mildly impaired subjects with fasting state stratification

Serum metabolomic biomarkers of perceptual speed in cognitively normal and mildly impaired subjects with fasting state stratification

A single meal has the potential to alter brain oxylipin content

Preventive Antibiotic Treatment Increases Neonatal Chicks Susceptibility to Salmonella Infection Via Disrupting Gut Microbiota and Linoleic Acid Metabolism

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