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Eicosapentaenoic Acid Reprograms Cerebrovascular Metabolism and Impairs Repair after Brain Injury, with Relevance to Chronic Traumatic Encephalopathy [mouse_brain_OnurE_RNA-seq]

ABSTRACT: Repetitive mild traumatic brain injury (rmTBI) precedes chronic traumatic encephalopathy (CTE) and involves neurovascular dysfunction. Omega-3 polyunsaturated fatty acids (PUFA) are promoted as neuroprotective, but long-term effects after brain injury remain uncertain. We uncover a metabolic vulnerability associated with cerebral accumulation of eicosapentaenoic acid (EPA), a major PUFA derived from fish oil. In a fish oil diet model, EPA accumulates at baseline yet is selectively depleted after rmTBI, consistent with mobilization during injury-associated metabolic remodeling. This pattern coincides with matrix remodeling, endothelial degeneration, and impaired neurovascular function. Cortical transcriptomics indicates reduced angiogenic programs with increased fatty acid metabolism, and lipidomics links EPA to maladaptive lipid engagement. Mechanistic studies using metabolically adapted endothelial cells show that EPA selectively impairs reparative function. Analysis of postmortem CTE brain tissue reveals parallel vascular and metabolic gene expression changes, strengthening translational relevance. Together, these findings challenge the assumption of uniform omega-3 neuroprotection after brain injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE319252 | GEO | 2026/02/11

REPOSITORIES: GEO

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Eicosapentaenoic Acid Reprograms Cerebrovascular Metabolism and Impairs Repair after Brain Injury, with Relevance to Chronic Traumatic Encephalopathy [human_brain_OnurE_RNA-seq]

Project description:Repetitive mild traumatic brain injury (rmTBI) precedes chronic traumatic encephalopathy (CTE) and involves neurovascular dysfunction. Omega-3 polyunsaturated fatty acids (PUFA) are promoted as neuroprotective, but long-term effects after brain injury remain uncertain. We uncover a metabolic vulnerability associated with cerebral accumulation of eicosapentaenoic acid (EPA), a major PUFA derived from fish oil. In a fish oil diet model, EPA accumulates at baseline yet is selectively depleted after rmTBI, consistent with mobilization during injury-associated metabolic remodeling. This pattern coincides with matrix remodeling, endothelial degeneration, and impaired neurovascular function. Cortical transcriptomics indicates reduced angiogenic programs with increased fatty acid metabolism, and lipidomics links EPA to maladaptive lipid engagement. Mechanistic studies using metabolically adapted endothelial cells show that EPA selectively impairs reparative function. Analysis of postmortem CTE brain tissue reveals parallel vascular and metabolic gene expression changes, strengthening translational relevance. Together, these findings challenge the assumption of uniform omega-3 neuroprotection after brain injury.

2026-02-11 | GSE319253 | GEO

Potential blood biomarkers for chronic traumatic encephalopathy: the multi-omics landscape of an observational cohort (serum exosomes miRNA microarray data)

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Evaluation of a high-EPA oil from transgenic Camelina sativa in feeds for Atlantic salmon (Salmo salar L.): Effects on tissue fatty acid composition, histology and gene expression

Project description:Currently, the only sustainable alternatives for dietary fish oil (FO) in aquafeeds are vegetable oils (VO) that are devoid of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA). Entirely new sources of n-3 LC-PUFA such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids through de novo production is a potential solution to fill the gap between supply and demand of these important nutrients. Camelina sativa,was metabolically engineered to produce a seed oil (ECO) with > 20 % EPA and its potential to substitute for FO in Atlantic salmon feeds was tested. Fish were fed one of three experimental diets containing FO, wild-type camelina oil (WCO) or ECO as the sole lipid sources for 7-weeks. Inclusion of ECO did not affect any of the performance parameters studied and enhanced apparent digestibility of individual n-6 and n-3 PUFA compared to dietary WCO. High levels of EPA were maintained in brain, liver and intestine (pyloric caeca), and levels of DPA and DHA were increased in liver and intestine of fish fed ECO compared to fish fed WCO likely due to increased LC-PUFA biosynthesis based on up-regulation of the genes. Fish fed WCO and ECO showed slight lipid accumulation within hepatocytes similar to that with WCO, although not significantly different to fish fed FO. The regulation of a small number of genes could be attributed to the specific effect of ECO (311 features) with metabolism being the most affected category. The EPA oil from transgenic Camelina (ECO) could be used as a substitute for FO, however it is a hybrid oil containing both FO (EPA) and VO (18:2n-6) fatty acid signatures that resulted in similarly mixed metabolic and physiological responses.

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Project description:Dietary supplementation with ω-3 polyunsaturated fatty acids (ω-3 PUFAs), specifically the fatty acids docosahexaenoic acid (DHA; 22:6 ω-3) and eicosapentaenoic acid (EPA; 20:5 ω-3), is known to have beneficial health effects including improvements in glucose and lipid homeostasis and modulation of inflammation. To evaluate the efficacy of two different sources of ω-3 PUFAs, we performed gene expression profiling in the liver of mice fed diets supplemented with either fish oil or krill oil. We found that ω-3 PUFA supplements derived from a phospholipid krill fraction (krill oil) downregulated the activity of pathways involved in hepatic glucose production as well as lipid and cholesterol synthesis. The data also suggested that krill oil-supplementation increases the activity of the mitochondrial respiratory chain. Surprisingly, an equimolar dose of EPA and DHA derived from fish oil modulated fewer pathways than a krill oil-supplemented diet and did not modulate key metabolic pathways regulated by krill oil, including glucose metabolism, lipid metabolism and the mitochondrial respiratory chain. Moreover, fish oil upregulated the cholesterol synthesis pathway, which was the opposite effect of krill supplementation. Neither diet elicited changes in plasma levels of lipids, glucose or insulin, probably because the mice used in this study were young and were fed a low fat diet. Further studies of krill oil supplementation using animal models of metabolic disorders and/or diets with a higher level of fat may be required to observe these effects.

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Nutritional evaluation of an EPA-DHA oil from transgenic Camelina sativa in feeds for post-smolt Atlantic salmon (Salmo salar L.)

Project description:Vegetable oils (VO) are possible substitutes for fish oil in aquafeeds but are limited by their lack of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA). However, oilseed crops can be modified to produce n-3 LC-PUFA such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, representing a potential option to fill the gap between supply and demand of these important nutrients. Camelina sativa was metabolically engineered to produce a seed oil with around 15 % total n-3 LC-PUFA to potentially substitute for fish oil in salmon feeds. Post-smolt Atlantic salmon (Salmo salar) were fed for 11-weeks with one of three experimental diets containing either fish oil (FO), wild-type Camelina oil (WCO) or transgenic Camelina oil (DCO) as added lipid source to evaluate fish performance, nutrient digestibility, tissue n-3 LC-PUFA, and metabolic impact determined by liver transcriptome analysis. The DCO diet did not affect any of the performance or health parameters studied and enhanced apparent digestibility of EPA and DHA compared to the WCO diet. The level of total n-3 LC-PUFA was higher in all the tissues of DCO-fed fish than in WCO-fed fish with levels in liver similar to those in fish fed FO. Endogenous LC-PUFA biosynthetic activity was observed in fish fed both the Camelina oil diets as indicated by the liver transcriptome and levels of intermediate metabolites such as docosapentaenoic acid, with data suggesting that the dietary combination of EPA and DHA inhibited desaturation and elongation activities. Expression of genes involved in phospholipid and triacylglycerol metabolism followed a similar pattern in fish fed DCO and WCO despite the difference in n-3 LC-PUFA contents.

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Project description:This study compared gene expression signatures between mice with repeated mild traumatic brain injury (rmtbi) and sham controls.

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Differential effects of krill oil and fish oil on the hepatic transcriptome in mice

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Expression data from hypothalamus of rats fed omega-3 or omega-6 essential fats

Project description:Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFA) have important signalling roles in the hypothalamus, a region of the brain that regulates whole-body energy homeostasis. While evidence suggests that high PUFA intake can impact hypothalamic activity, the underlying molecular mechanisms regulated by essential dietary PUFA (i.e., linoleic acid and alpha-linolenic acid) remain poorly described in this brain region. To differentiate the roles of essential dietary PUFA on hypothalamic function, we fed male rats high-fat diets (35% kcal/d) containing either safflower (linoleic acid) or flaxseed (alpha-linolenic acid) oil for 2 months. Control rats were fed a low-fat (16% kcal/d) diet containing soybean oil. Hypothalmic gene expression was investigated by microrray.

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