Contribution of Poly-unsaturated Fatty Acids on Cerebral Neurobiology: An Integrated Omics Approach with Epigenomic Focus
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE83545 | GEO | 2017/07/31
SECONDARY ACCESSION(S): PRJNA326279
REPOSITORIES: GEO
Similar Datasets
Project description:The epigenetic landscape is vulnerable to variations in diet. Here, we investigated the influence of different PUFA dietary supplements on rodents’ nervous system development and functions and potential consequences for neurodegenerative disorders. We have previously studied the genomic plasticity of these biofunctions in mice fed on high n-3 PUFA enriched diet (ERD). In conjunction, in the present study, we introduced a second equicaloric diet with n-3 PUFA optimally balanced by n-6 PUFA (BLD). The typical lab diet with high n-6 PUFA was the baseline. Randomly grouped C57BL/6j mice were fed on any of these three diets from their neonatal age to late adolescent. Post-euthanasia, the transcriptomic landscape of hemibrains was investigated in parallel for two epigenetic mechanisms, namely the miRNA profile and DNA methylation. Integrating data we focused on those genes which had both hypermethylated CpG islands and silenced transcripts. Of these, 308 and 131 genes were perturbed by ERD and BLD, respectively, in comparison to the baseline. Also, miRNA:mRNA pairs were screened to identify those overexpressed miRNAs that silenced gene transcription. There were 18 and 39 miRNAs that met the cutoff in ERD- and BLD-fed mice, respectively. The majority of miRNAs overexpressed by BLD are associated with Alzheimer’s and schizophrenia. BLD allowed hypermethylation of those genes that enriched the networks associated with calcium-releasing neurotransmitters. Downstream networks leading to LTP, memory, cognition and learning were perturbed in sync. ERD permitted hypermethylation of genes that enrich the cytoskeletal development network and promote the formation of neuronal precursors. We present the conclusions taking into full account the limited knowledge regarding the epigenetic influence on biofunctions. Since this study has single time point, we could not verify if these functional attributes are the cause or the consequences of epigenetic plasticity. Hence, a more comprehensive study in this regard is essential.
2017-07-31 | GSE83544 | GEO
Project description:Fish oil or its major constituent, namely omega-3 poly-unsaturated fatty acid (n3-PUFA), are popular diets to improve neurogenesis, neuroprotection, and overall brain functions. A growing number of studies advocate for the balanced dietary supplements of n3- and n6-PUFA to maximize the brain functions. Our objective was to probe the implication of PUFA to ameliorate social stress (SS). Mice were fed a customized n-3 PUFA-enriched diet (ERD, n3:n6= 7:1), a balanced diet (BLD, n3:n6= 1:1) or a standard lab diet (STD, n3:n6= 1:6). Past reports linked these diets to brain transcriptomic regulations; hence, we aimed to investigate the effects of these diets on mice exposed to Aggressor-exposed SS (Agg-E SS) model. Mice randomly encountered life-threatening trauma from conspecific aggressor for 10 consecutive days. Stressed mice on STD showed multiple behavioral deficits that lingered even 6 weeks post-Agg-E SS. In comparison, ERD and BLD elevated bodyweights but potentially triggered behavioral resilience to SS. Comprehensive mapping of the behavioral traits projected a diet-specific variance, which was mirrored by the brain transcriptomic readouts. We focused on those brain transcriptomic networks that were exclusively perturbed by the cumulative effects of Diet, Stress and Time. STD adversely affected the gene networks associated with the cell mortality, energy homeostasis and neurodevelopment disorder; however, BLD showed long-term benefits in regulating these gene networks. Further titration of PUFA supplements in daily diets can reduce the adverse effects caused by unbalanced supplement of PUFA without compromising their health benefits.
2023-03-15 | GSE204718 | GEO
Project description:The epigenetic landscape is vulnerable to variations in diet. Here, we investigated the influence of different PUFA dietary supplements on rodents’ nervous system development and functions and potential consequences for neurodegenerative disorders. We have previously studied the genomic plasticity of these biofunctions in mice fed on high n-3 PUFA enriched diet (ERD). In conjunction, in the present study, we introduced a second equicaloric diet with n-3 PUFA optimally balanced by n-6 PUFA (BLD). The typical lab diet with high n-6 PUFA was the baseline. Randomly grouped C57BL/6j mice were fed on any of these three diets from their neonatal age to late adolescent. Post-euthanasia, the transcriptomic landscape of hemibrains was investigated in parallel for two epigenetic mechanisms, namely the miRNA profile and DNA methylation. Integrating data we focused on those genes which had both hypermethylated CpG islands and silenced transcripts. Of these, 308 and 131 genes were perturbed by ERD and BLD, respectively, in comparison to the baseline. Also, miRNA:mRNA pairs were screened to identify those overexpressed miRNAs that silenced gene transcription. There were 18 and 39 miRNAs that met the cutoff in ERD- and BLD-fed mice, respectively. The majority of miRNAs overexpressed by BLD are associated with Alzheimer’s and schizophrenia. BLD allowed hypermethylation of those genes that enriched the networks associated with calcium-releasing neurotransmitters. Downstream networks leading to LTP, memory, cognition and learning were perturbed in sync. ERD permitted hypermethylation of genes that enrich the cytoskeletal development network and promote the formation of neuronal precursors. We present the conclusions taking into full account the limited knowledge regarding the epigenetic influence on biofunctions. Since this study has single time point, we could not verify if these functional attributes are the cause or the consequences of epigenetic plasticity. Hence, a more comprehensive study in this regard is essential.
2017-07-31 | GSE83543 | GEO
Project description:Contribution of Poly-unsaturated Fatty Acids on Cerebral Neurobiology: An Integrated Omics Approach with Epigenomic Focus
| PRJNA326279 | ENA
Project description:Contribution of Poly-unsaturated Fatty Acids on Cerebral Neurobiology: An Integrated Omics Approach with Epigenomic Focus [Agilent]
| PRJNA842008 | ENA
Project description:While the impact of dietary cholesterol on the progression of atherosclerosis has probably been overestimated, increasing evidence suggests that dietary cholesterol might favor the transition from blunt steatosis to non-alcoholic steatohepatitis (NASH), especially in combination with high fat diets. It is poorly understood how cholesterol alone or in combination with other dietary lipid components contributes to the development of lipotoxicity. The current study demonstrated that liver damage caused by dietary cholesterol in mice was strongly enhanced by a high fat diet containing soybean oil-derived ω6-poly-unsaturated fatty acids (ω6-PUFA), but not by a lard-based high fat diet containing mainly saturated fatty acids. In contrast to the lard-based diet the soybean oil-based diet augmented cholesterol accumulation in hepatocytes, presumably by impairing cholesterol-eliminating pathways. The soybean oil-based diet enhanced cholesterol-induced mitochondrial damage and amplified the ensuing oxidative stress, probably by peroxidation of poly-unsaturated fatty acids. This resulted in hepatocyte death, recruitment of inflammatory cells, and fibrosis, and caused a transition from steatosis to NASH, doubling the NASH activity score. Thus, the recommendation to reduce cholesterol intake, in particular in diets rich in ω6-PUFA, although not necessary to reduce the risk of atherosclerosis, might be sensible for patients suffering from non-alcoholic fatty liver disease.
| S-EPMC6164134 | biostudies-literature
Project description:Although evidence has shown the regulating effect of n-3 poly-unsaturated fatty acid (n-3 PUFA) on cell signaling transduction, it remains unknown whether n-3 PUFA treatment modulates estrogen signaling. The current study showed that docosahexaenoic acid (DHA, C22:6), eicosapentaenoic acid (EPA, C20:5) shifted the pro-survival and proliferative effect of estrogen to a pro-apoptotic effect in human breast cancer (BCa) MCF-7 and T47D cells. 17 ?-estradiol (E2) enhanced the inhibitory effect of n-3 PUFAs on BCa cell growth. The IC50 of DHA or EPA in MCF-7 cells decreased when combined with E2 (10 nM) treatment (from 173 µM for DHA only to 113 µM for DHA+E2, and from 187 µm for EPA only to 130 µm for EPA+E2). E2 also augmented apoptosis in n-3 PUFA-treated BCa cells. In contrast, in cells treated with stearic acid (SA, C18:0) as well as cells not treated with fatty acid, E2 promoted breast cancer cell growth. Classical (nuclear) estrogen receptors may not be involved in the pro-apoptotic effects of E2 on the n-3 PUFA-treated BCa cells because ER? agonist failed to elicit, and ER? knockdown failed to block E2 pro-apoptotic effects. Subsequent studies reveal that G protein coupled estrogen receptor 1 (GPER1) may mediate the pro-apoptotic effect of estrogen. N-3 PUFA treatment initiated the pro-apoptotic signaling of estrogen by increasing GPER1-cAMP-PKA signaling response, and blunting EGFR, Erk 1/2, and AKT activity. These findings may not only provide the evidence to link n-3 PUFAs biologic effects and the pro-apoptotic signaling of estrogen in breast cancer cells, but also shed new insight into the potential application of n-3 PUFAs in BCa treatment.
| S-EPMC3532062 | biostudies-literature
Project description:To obtain mechanistic insights into the cross talk between lipolysis and autophagy, two key metabolic responses to starvation, we screened the autophagy-inducing potential of a panel of fatty acids in human cancer cells. Both saturated and unsaturated fatty acids such as palmitate and oleate, respectively, triggered autophagy, but the underlying molecular mechanisms differed. Oleate, but not palmitate, stimulated an autophagic response that required an intact Golgi apparatus. Conversely, autophagy triggered by palmitate, but not oleate, required AMPK, PKR and JNK1 and involved the activation of the BECN1/PIK3C3 lipid kinase complex. Accordingly, the downregulation of BECN1 and PIK3C3 abolished palmitate-induced, but not oleate-induced, autophagy in human cancer cells. Moreover, Becn1(+/-) mice as well as yeast cells and nematodes lacking the ortholog of human BECN1 mounted an autophagic response to oleate, but not palmitate. Thus, unsaturated fatty acids induce a non-canonical, phylogenetically conserved, autophagic response that in mammalian cells relies on the Golgi apparatus.
| S-EPMC4406650 | biostudies-literature
Project description:Oils are an essential part of the human diet and are primarily derived from plant (or sometimes fish) sources. Several of them exhibit anti-inflammatory properties. Specific diets, such as Mediterranean diet, that are high in ω-3 polyunsaturated fatty acids (PUFAs) and ω-9 monounsaturated fatty acids (MUFAs) have even been shown to exert an overall positive impact on human health. One of the most widely used supplements in the developed world is fish oil, which contains high amounts of PUFAs docosahexaenoic and eicosapentaenoic acid. This review is focused on the natural sources of various polyunsaturated and monounsaturated fatty acids in the human diet, and their role as precursor molecules in immune signaling pathways. Consideration is also given to their role in CNS immunity. Recent findings from clinical trials utilizing various fatty acids or diets high in specific fatty acids are reviewed, along with the mechanisms through which fatty acids exert their anti-inflammatory properties. An overall understanding of diversity of polyunsaturated fatty acids and their role in several molecular signaling pathways is useful in formulating diets that reduce inflammation and increase longevity.
| S-EPMC9953405 | biostudies-literature
Project description:Fatty acid desaturase 2 (fads2) is one of the rate-limiting enzymes in PUFAs biosynthesis. Compared with the diploid fish encoding one fads2, the allo-tetraploid common carp, one most important food fish, encodes two fads2 genes (fads2a and fads2b). The associations between the contents of different PUFAs and the polymorphisms of fads2a and fads2b have not been studied. The contents of 12 PUFAs in common carp individuals were measured, and the polymorphisms in the coding sequences of fads2a and fads2b were screened. We identified five coding single nucleotide polymorphisms (cSNPs) in fads2a and eleven cSNPs in fads2b. Using the mixed linear model and analysis of variance, a synonymous fads2a cSNP was significantly associated with the content of C20:3n-6. One non-synonymous fads2b cSNP (fads2b.751) and one synonymous fads2b cSNP (fads2b.1197) were associated with the contents of seven PUFAs and the contents of six PUFAs, respectively. The heterozygous genotypes in both loci were associated with higher contents than the homozygous genotypes. The fads2b.751 genotype explained more phenotype variation than the fads2b.1197 genotype. These two SNPs were distributed in one haplotype block and associated with the contents of five common PUFAs. These results suggested that fads2b might be the major gene responding to common carp PUFA contents and that fads.751 might be the main effect SNP. These cSNPs would be potential markers for future selection to improve the PUFA contents in common carp.
| S-EPMC8232129 | biostudies-literature