Dietary long-chain omega 3 fatty acids modify sphingolipid metabolism to facilitate asthmatic airway hyperreactivity
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE203418 | GEO | 2022/08/01
REPOSITORIES: GEO
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Project description:Fish oil, olive oil, and coconut oil dietary supplementation have several cardioprotective benefits, but it is not established if they can protect against air pollution-induced adverse effects. We hypothesized that these dietary supplements would attenuate ozone-induced systemic and pulmonary effects. Male Wistar Kyoto rats were fed either a normal diet, or a diet enriched with fish, olive, or coconut oil starting at 4 weeks of age for 8 weeks. Animals were then exposed to air or ozone (0.8 ppm), 4h/day for 2 consecutive days. The fish oil diet completely abolished phenylephrine-induced vasoconstriction that was increased following ozone exposure in the animals fed all other diets. Only the fish oil diet increased baseline levels of bronchoalveolar lavage fluid (BALF) markers of lung injury and inflammation. Ozone-induced pulmonary injury/inflammation were comparable in rats on normal, coconut oil, and olive oil diets with altered expression of markers in animals fed the fish oil diet. Fish oil, regardless of exposure, led to enlarged, foamy macrophages in the BALF that coincided with decreased mRNA expression of cholesterol transporters, cholesterol receptors, and nuclear receptors in the lung. Serum miRNA profile was assessed using small RNA-sequencing in normal and fish oil groups and demonstrated marked depletion of a variety of miRNAs, several of which were of splenic origin. No ozone-specific changes were noted. Collectively, these data indicate that while fish oil offered protection from ozone-induced aortic vasoconstriction, it increased pulmonary injury/inflammation and impaired lipid transport mechanisms resulting in foamy macrophage accumulation, demonstrating the need to be cognizant of potential off-target pulmonary effects that might offset the overall benefit of this vasoprotective dietary supplement.
2018-01-11 | GSE102015 | GEO
Project description:We used DNA microarrays to identify discriminative gene signatures for the purpose of classifying n-3 PUFA-fed, carcinogen injected Sprague Dawley rats at the initiation and progression stages. Animals were assigned to three dietary treatments differeing only in the type of fat (corn oi/n-6 PUFA, fish oil/n-3 PUFA, or olive oli/n-9 monounsaturated fatty acid). The effects of diet on colonic mucosal gene expression signatures during tumor initiation with the progression of colon cancer. Each dietary lipid source exhibited its own unique transcriptional profile, as assessed by linear discriminant analysis. Applying this novel approach we identified the single genes and the two- to three-gene combinations that best distinguished the dietary treatment groups. For the chemoprotective fish oil diet, mediators of stem cell homeostasis, e.g., ephrin B1 and bone morphogenic protein 4, were the top-permorming gene classifiers. keywords: diet analysis 29 samples were analyzed. 10 samples had repeat arrays. No control or reference samples were included.
2010-12-09 | E-GEOD-25912 | biostudies-arrayexpress
Project description:Obesity exacerbates inflammation upon lung injury; however, the mechanisms by which obesity primes pulmonary dysregulation prior to injury are not well studied. Notably, little is known about how obesity dysregulates pulmonary polyunsaturated fatty acid (PUFA) metabolism that is central to inflammation initiation and resolution. Herein, we first show that a high fat diet (HFD) administered to C57BL/6J mice increases the relative abundance of pulmonary PUFA-containing triglycerides and the concentration of PUFA-derived oxylipins, independent of an increase in total pulmonary PUFAs, prior to onset of pulmonary inflammation. Experiments with a genetic model of obesity did not recapitulate the effects of the HFD on the pulmonary oxylipin signature, revealing a diet-driven effect. Subsequent pulmonary next-generation RNA sequencing identified complex and unique transcriptional regulation with the HFD. The HFD increased pathways related to glycerophospholipid metabolism and immunity, including an elevation in B cell differentiation and signaling. Finally, computational integration of lipidomic with transcriptomic data revealed novel HFD-driven networks between glycerophospholipid metabolism and B cell receptor signaling with specific PUFA-derived oxylipins. Collectively, these data show obesity dysregulates pulmonary PUFA metabolism prior to lung injury, which may be a mechanism by which obesity primes the lungs to respond poorly upon infectious and/or inflammatory challenges.
2022-09-28 | GSE194403 | GEO
Project description:We used DNA microarrays to identify discriminative gene signatures for the purpose of classifying n-3 PUFA-fed, carcinogen injected Sprague Dawley rats at the initiation and progression stages. Animals were assigned to three dietary treatments differeing only in the type of fat (corn oi/n-6 PUFA, fish oil/n-3 PUFA, or olive oli/n-9 monounsaturated fatty acid). The effects of diet on colonic mucosal gene expression signatures during tumor initiation with the progression of colon cancer. Each dietary lipid source exhibited its own unique transcriptional profile, as assessed by linear discriminant analysis. Applying this novel approach we identified the single genes and the two- to three-gene combinations that best distinguished the dietary treatment groups. For the chemoprotective fish oil diet, mediators of stem cell homeostasis, e.g., ephrin B1 and bone morphogenic protein 4, were the top-permorming gene classifiers. keywords: diet analysis
2010-12-09 | GSE25912 | GEO
Project description:Asthma is typically characterized by an imbalance between the expression of proteases and of inhibitors capable of neutralizing such enzymes. Hence, an attractive option for intervening with asthma could be to interfere with asthma-associated proteases. In this study, we exploited this option by assessing the impact of nafamostat, a serine protease inhibitor with known capacity to neutralize mast cell tryptase, on the manifestations of airway responses in a house dust mite (HDM)-based model of experimental asthma. Our findings reveal that nafamostat efficiently suppressed the airway hyperreactivity in HDM-sensitized mice, which was accompanied by a profound reduction in the infiltration of eosinophils and lymphocytes to the airways, and also by suppression of the levels of proinflammatory compounds within the airway lumen.Further, nafamostat caused a marked reduction of eosinophil inflammation in the lung tissue, and we also show that nafamostat had a dampening impact on goblet cell hyperplasia and smooth muscle layer thickening in the lungs of HDM-sensitized animals. To obtain deeper insight into the mechanism by which nafamostat affects parameters of allergic airway inflammation, a transcriptomic analysis was conducted. This analysis revealed, as expected, that the HDM sensitization caused an upregulated expression of numerous proinflammatory genes. Further, the transcriptomic analysis showed that nafamostat suppressed the levels of multiple proinflammatory genes, with a particular impact on genes related to asthma. Altogether, this study provides extensive insight into the ameliorating effect of nafamostat on experimental asthma, and our findings can thereby provide a basis for the further evaluation of nafamostat as a potential therapeutic agent in human asthma.
2023-05-10 | GSE223629 | GEO
Project description:Obesity is associated with severe, difficult to control asthma, and increased airway oxidative stress. Mitochondrial reactive oxygen species (mROS) are an important source of oxidative stress leading us to hypothesize that targeting mROS in obese allergic asthma might be an effective treatment strategy. Using a mouse model of house dust mite (HDM) induced allergic airway disease in mice fed a low- (LFD) or high-fat diet (HFD), and the mitochondrial antioxidant MitoQuinone (MitoQ); we investigated the effects of obesity and mROS on airway inflammation, remodelling and airway hyperreactivity (AHR). HDM induces airway inflammation, remodelling and hyperreactivity in both lean and obese mice. Obese allergic mice showed increased lung tissue eotaxin levels, airway tissue eosinophilia and AHR when compared to lean allergic mice. MitoQ reduced markers of airway inflammation, remodelling and hyperreactivity in both lean and obese allergic mice, and tissue eosinophilia in obeseHDM mice. mROS regulates cell signalling by protein oxidation of multiple downstream targets: MitoQ reduced HDM-induced cysteine-sulfenylation of several proteins including those involved in the unfolded protein response (UPR). In summary, mROS mediates the development of allergic airway disease and hence MitoQ might be effective for the treatment for asthma, and specific features of obese asthma.
2023-06-02 | PXD029715 | Pride
Project description:In a randomized controlled dietary intervention study, we compared a diet enriched in polyunsaturated fatty acids (PUFA) with a diet enriched in saturated fatty acids (SFA) for influence on abdominal subcutaneous adipose tissue gene expression. We studied young lean adults; 11 women and 25 men. There was no significant difference in age, BMI, or gene expression between the PUFA and SFA groups before the intervention. The intervention lasted for seven weeks. We calculated for each gene the absolute difference in gene expression after vs. before intervention (deltas), and compared the deltas between the PUFA and SFA group using SAM. 12 genes were significantly differentially regulated by the two diets with a FDR of 25%. These include metabolic and adipokine genes. In conclusion, dietary fatty acids have a modest influence on white adipose tissue gene expression.
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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.
2018-08-29 | GSE104338 | GEO
Project description:The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is associated with abnormalities of liver lipid metabolism, especially with the accumulation of saturated fatty acids (FA). On the contrary, a diet enriched with n-3 polyunsaturated FA (n-3-PUFA) has been reported to ameliorate the progression of NAFLD. The aim of our study was to investigate the impact of dietary n-3-PUFA enrichment on the development of NAFLD and liver lipidome. Mice were fed for 6 weeks either high-fat methionine choline-deficient diet (MCD) or standard chow (two groups fed MCD, two control groups, both with or without n-3-PUFA). Genome-wide transcriptome analysis of liver tissue was performed and revealed differences in liver mRNA transcriptomes after MCD as well as n-3-PUFA administration.
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2018-03-01 | PXD004114 | Pride