Maternal n-3 PUFAs deficiency regulates gene expression profile in microglia at P21 in offspring
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE158181 | GEO | 2020/10/20
REPOSITORIES: GEO
Similar Datasets
Project description:Maternal n-3 PUFAs deficiency regulates gene expression profile in microglia at P21 in offspring
| PRJNA664213 | ENA
Project description:<p>Omega-3 fatty acids (n-3 polyunsaturated fatty acids; n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in epidemiological studies, but the mechanisms by which a n-3 PUFA dietary imbalance affects CNS development are poorly understood. Active microglial engulfment of synaptic elements is an important process for normal brain development and altered synapse refinement is a hallmark of several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development. Our results show that maternal dietary n-3 PUFA deficiency increases microglial phagocytosis of synaptic elements in the developing hippocampus, partly through the activation of 12/15- lipoxygenase (LOX)/12-HETE signaling, which alters neuronal morphology and affects cognition in the postnatal offspring. While women of child bearing age are at higher risk of dietary n-3 PUFA deficiency, these findings provide new insights into the mechanisms linking maternal nutrition to neurodevelopmental disorders.</p>
2020-11-03 | MTBLS1952 | MetaboLights
Project description:The evolution of human diets led to preferences towards polyunsaturated fatty acid (PUFA) content with ‘Western’ diets enriched in w-6 PUFA1. Mounting evidence points to w-6 PUFA excess limiting metabolic and cognitive processes that define longevity in humans2. When chosen during pregnancy, w-6 PUFA-enriched ‘Western’ diets can reprogram maternal bodily metabolism with maternal nutrient supply precipitating the body-wide imprinting of molecular and cellular adaptations at the level of long-range intercellular signaling networks in the unborn fetus2,3. Even though unfavorable neurological outcomes are amongst the most common complications of intrauterine w-6 PUFA excess3, cellular underpinnings of life-long modifications to brain architecture remain unknown. Here, we show that nutritional w-6 PUFA-derived endocannabinoids desensitize CB1 cannabinoid receptors, thus inducing epigenetic repression of transcriptional regulatory networks controlling neuronal differentiation. We found that cortical neurons lose their positional identity and axonal selectivity once exposing mouse fetuses to excess w-6 PUFAs in utero. Conversion of w-6 PUFAs into endocannabinoids disrupted the temporal precision of signaling at neuronal CB1 cannabinoid receptors, chiefly deregulating Stat3-dependent transcriptional cascades otherwise required to execute neuronal differentiation programs. Global proteomics identified the immunoglobulin family of cell adhesion molecules (IgCAMs) as direct substrates with DNA methylome analysis and ATAC-seq uncovering epigenetic reprogramming at >1,400 sites in neurons after prolonged cannabinoid exposure. We find anxiety and depression-like behavioral traits to manifest in adult offspring, which is compatible with genetic models of reduced IgCAM expression to suggest causality to cortical wiring defects4. Overall, our data uncover a regulatory mechanism whose disruption by maternal food choices could limit the offsprings’ brain function for life.
2019-11-21 | PXD016180 | Pride
Project description:The evolution of human diets led to preferences towards polyunsaturated fatty acid (PUFA) content with ‘Western’ diets enriched in ω-6 PUFAs. Mounting evidence points to ω-6 PUFA excess limiting metabolic and cognitive processes that define longevity in humans. When chosen during pregnancy, ω-6 PUFA-enriched ‘Western’ diets can reprogram maternal bodily metabolism with maternal nutrient supply precipitating the body-wide imprinting of molecular and cellular adaptations at the level of long-range intercellular signaling networks in the unborn fetus. Even though unfavorable neurological outcomes are amongst the most common complications of intrauterine ω6 PUFA excess, cellular underpinnings of life-long modifications to brain architecture remain unknown. Here, we show that nutritional ω-6 PUFA-derived endocannabinoids desensitize CB1 cannabinoid receptors, thus inducing epigenetic repression of transcriptional regulatory networks controlling neuronal differentiation. We found that cortical neurons lose their positional identity and axonal selectivity when mouse fetuses are exposed to excess ω-6 PUFAs in utero. Conversion of ω-6 PUFAs into endocannabinoids disrupted the temporal precision of signaling at neuronal CB1 cannabinoid receptors, chiefly deregulating Stat3-dependent transcriptional cascades otherwise required to execute neuronal differentiation programs. Global proteomics identified the immunoglobulin family of cell adhesion molecules (IgCAMs) as direct substrates, with DNA methylation and chromatin accessibility profiling uncovering epigenetic reprogramming at >1,400 sites in neurons after prolonged cannabinoid exposure. We found anxiety and depression-like behavioral traits to manifest in adult offspring, which is consistent with genetic models of reduced IgCAM expression, to suggest causality for cortical wiring defects. Overall, our data uncover a regulatory mechanism whose disruption by maternal food choices could limit an offspring’s brain function for life.
2019-11-08 | GSE140081 | GEO
Project description:The evolution of human diets led to preferences towards polyunsaturated fatty acid (PUFA) content with ‘Western’ diets enriched in ω-6 PUFAs. Mounting evidence points to ω-6 PUFA excess limiting metabolic and cognitive processes that define longevity in humans. When chosen during pregnancy, ω-6 PUFA-enriched ‘Western’ diets can reprogram maternal bodily metabolism with maternal nutrient supply precipitating the body-wide imprinting of molecular and cellular adaptations at the level of long-range intercellular signaling networks in the unborn fetus. Even though unfavorable neurological outcomes are amongst the most common complications of intrauterine ω6 PUFA excess, cellular underpinnings of life-long modifications to brain architecture remain unknown. Here, we show that nutritional ω-6 PUFA-derived endocannabinoids desensitize CB1 cannabinoid receptors, thus inducing epigenetic repression of transcriptional regulatory networks controlling neuronal differentiation. We found that cortical neurons lose their positional identity and axonal selectivity when mouse fetuses are exposed to excess ω-6 PUFAs in utero. Conversion of ω-6 PUFAs into endocannabinoids disrupted the temporal precision of signaling at neuronal CB1 cannabinoid receptors, chiefly deregulating Stat3-dependent transcriptional cascades otherwise required to execute neuronal differentiation programs. Global proteomics identified the immunoglobulin family of cell adhesion molecules (IgCAMs) as direct substrates, with DNA methylation and chromatin accessibility profiling uncovering epigenetic reprogramming at >1,400 sites in neurons after prolonged cannabinoid exposure. We found anxiety and depression-like behavioral traits to manifest in adult offspring, which is consistent with genetic models of reduced IgCAM expression, to suggest causality for cortical wiring defects. Overall, our data uncover a regulatory mechanism whose disruption by maternal food choices could limit an offspring’s brain function for life.
2019-11-08 | GSE140080 | GEO
Project description:To further understand the molecular mechanisms underlying the health effects of replacing saturated fat (SFA) with polyunsaturated fat (PUFA), we aimed to explore the whole transcriptome response of peripheral blood mononuclear cells (PBMCs) in a dietary intervention where SFAs were replaced with PUFAs.
2021-06-03 | GSE176043 | GEO
Project description:We report the effects of dietary n-3 polyunsaturated fatty acids (PUFAs) on sphingolipid metabolism and airway reactivity in the lung. Mice were fed a n3-PUFA enriched fishoil diet or an isocaloric control coconut oil-enriched diet (CO) for 8 weeks. The n-3 PUFA diet affected pulmonary sphingolipid metabolism, and airway reactivity, independent of inflammation or allergic sensitization. These findings support a role for pulmonary sphingolipid homeostasis in asthma and could have implications for the use of n-3 PUFA dietary supplements in asthma.
2022-08-01 | GSE203418 | GEO
Project description:Within the secreted phospholipase A2 (sPLA2) family, group X sPLA2 (sPLA2-X) has the highest capacity to hydrolyze cellular membranes and has long been thought to promote inflammation by releasing arachidonic acid (AA), a precursor of pro-inflammatory eicosanoids. Unexpectedly, we found that transgenic mice globally overexpressing human sPLA2-X (PLA2G10-Tg) displayed striking immunosuppressive and lean phenotypes with lymphopenia and increased M2-like macrophages, accompanied by marked elevation of free omega-3 polyunsaturated fatty acids (PUFAs) and their metabolites. Studies using Pla2g10-deficient mice revealed that endogenous sPLA2-X, which is highly expressed in the colon epithelium and spermatozoa, mobilized omega-3 PUFAs or their metabolites to protect against dextran sulfate sodium (DSS)-induced colitis and to promote fertilization, respectively. In colitis, sPLA2-X deficiency increased colorectal expression of Th17 cytokines, and omega-3 PUFAs attenuated their production by lamina propria cells partly through the fatty acid receptor GPR120. In comparison, cytosolic phospholipase A2 (cPLA2alpha) protects from colitis by mobilizing omega-6 AA metabolites including prostaglandin E2. Thus, our results underscore a previously unrecognized role of sPLA2-X as an omega-3 PUFA mobilizer in vivo, segregated mobilization of omega-3 and omega-6 PUFA metabolites by sPLA2-X and cPLA2alpha, respectively, in protection against colitis, and the novel role of a particular sPLA2-X-driven PUFA in fertilization.
2016-02-01 | GSE77144 | GEO
Project description:Experimental studies confirmed n-6 type polyunsaturated fatty acid as pro-carcinogenic factor and n-3 fatty acid as cancer restraining agent; though their mode of action on tumor cells are still unclear. To review the contrasting effect of omega-3 and omega-6 fatty acids over carcinoma by studying genomic alteration in treated cancer cells, two members from each family of PUFAs, namely EPA and DHA from n-3 PUFA family and, AA and LA from n-6 PUFA family was selected to treat four breast cancer cell lines: MDA-MB231, MDA-MB435S, HCC2218 and MCF-7 for two time period- 6hr and 24hr.
2006-03-29 | E-GEOD-4497 | biostudies-arrayexpress
Project description:Atlantic salmon can synthesize polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (20:5n-3), arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) via activities of very long chain fatty acyl elongases (elovls) and fatty acyl desaturases (fads), albeit to a limited degree. Understanding molecular mechanisms of PUFA biosynthesis and regulation is a pre-requisite for sustainable use of vegetable oils in aquafeeds as current sources of fish oils are unable to meet increasing demands for omega-3 PUFAs. By generating CRISPR-mediated elovl2 knockout, we have shown that elovl2 is crucial for multi-tissue synthesis of 22:6n-3 in vivo and endogenously synthesized PUFAs are important for transcriptional regulation of lipogenic genes in Atlantic salmon. The elovl2 knockouts showed reduced levels of 22:6n-3 and accumulation of 20:5n-3 and docosapentaenoic acid (22:5n-3) in the liver, brain and white muscle, suggesting inhibition of elongation. Additionally, elovl2-knockout salmon showed accumulation of 20:4n-6 in the brain and white muscle. The impaired synthesis of 22:6n-3 induced hepatic expression of sterol regulatory element binding protein-1 (srebp-1), fatty acid synthase-b, Δ6fad-a, Δ5fad and elovl5. Our study demonstrates key roles of elovl2 at two penultimate steps of PUFA synthesis in vivo and suggests Srebp-1 as a main regulator of PUFA synthesis in Atlantic salmon.
2019-04-30 | E-MTAB-7220 | biostudies-arrayexpress