GNPS Alterations in fatty acids in NPC1
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Agilent 6550 QTOF
ORGANISM(S): Homo Sapiens (ncbitaxon:9606) Mus Musculus (ncbitaxon:10090)
SUBMITTER: 
Stephanie Cologna
PROVIDER: MSV000086932 | GNPS | Mon Feb 22 15:04:00 GMT 2021
REPOSITORIES: GNPS
Similar Datasets
Project description:We report a conserved transcriptomic signature of reduced fatty acid and lipid metabolism gene expression in human post-mortem ALS spinal cord and a Drosophila model of the most common genetic cause of FTD/ALS, a repeat expansion in C9orf72. To investigate lipid alterations, we performed lipidomics on C9FTD/ALS iPSC-neurons and post-mortem FTLD brain tissue. This revealed a common and specific reduction in phospholipid species containing polyunsaturated fatty acids (PUFAs). To determine whether this PUFA deficit contributes to neurodegeneration, we fed C9FTD/ALS flies PUFAs, which yielded a modest increase in survival. However, increasing PUFA levels specifically in neurons of the C9orf72 flies, by overexpressing fatty acid desaturase enzymes, led to a substantial extension of lifespan. Neuronal overexpression of fatty acid desaturases also suppressed stressor induced neuronal death in C9FTD/ALS patient iPSC-neurons. These data implicate neuronal fatty acid saturation in the pathogenesis of FTD/ALS and suggest that interventions to increase PUFA levels specifically within neurons will be beneficial.
2024-11-15 | GSE255099 | GEO
Project description:Triglyceride-rich lipoproteins and their remnants contribute to atherosclerosis, possibly by carrying remnant cholesterol and/or by exerting a pro-inflammatory effect on macrophages. Nevertheless, little is known about how macrophages process triglyceride-rich lipoproteins. We show that uptake by macrophages of VLDL-sized emulsion particles is dependent on the enzyme lipoprotein lipase via its C-terminal domain. Subsequent internalization of VLDL-triglycerides by macrophages is carried out by caveolae-mediated endocytosis, followed by hydrolysis by lysosomal acid lipase. STARD3 is required for the transfer of lysosomal fatty acids to the ER for lipid storage, while NPC1 likely is involved in promoting the extracellular efflux of fatty acids. Our data provide novel insights into how macrophages process VLDL-derived triglycerides and suggest that macrophages have the remarkable capacity to excrete internalized triglycerides as fatty acids.
2022-05-21 | GSE203250 | GEO
Project description:Arabidopsis seeds expressing the castor fatty acid hydroxylase accumulate hydroxylated fatty acids up to 17% of total fatty acids in seed triacylglycerols, however total seed oil is also reduced up to 50%. Investigations into the cause of the reduced oil phenotype through in vivo [14C]acteate and [3H]2O metabolic labeling of developing seeds surprisingly revealed that the rate of de novo fatty acid synthesis within the transgenic seeds was approximately half that of control seeds. Addition of castor phospholipid:diacylglycerol acyltransferase (PDAT) increased hydroxylated fatty acid content of the seed oil, increased the rate of fatty acid synthesis, and mostly restored seed oil levels. RNAseq analysis indicated no changes in expression of fatty acid synthesis genes in hydroxylase-expressing plants. Transcript profiles of Arabidopsis developing seeds of three lines, at three stages of development were generated by deep sequencing, in triplicate, using Illumina.
2014-01-10 | E-GEOD-53952 | biostudies-arrayexpress
Project description:Purkinje cells (PC) of the cerebellum degenerate in adult mice with mutations in the Niemann-Pick type C (NPC) disease 1 (Npc1) gene. We subjected BALB/c Npc1+/+ and Npc1-/- mouse cerebella from an early and a later time point of PC degeneration to a genome-wide microarray gene expression analysis. We found general underrepresentation of PC-specific transcripts, consistent with PC loss, and elevated markers of microglia activation at the later time point. Experiment Overall Design: 12 BALB/c Npc1 mice of the two ages P21 and P49 and the two genotypes Npc1+/+ and Npc1-/- were used, 3 replicates for each age and genotype. The animals were of the same breed and lived under identical housing conditions. All except one animal were female. The animals were not further treated, but only sacrificed at P21 or P49.
2008-06-14 | E-GEOD-5944 | biostudies-arrayexpress
Project description:Arabidopsis seeds expressing the castor fatty acid hydroxylase accumulate hydroxylated fatty acids up to 17% of total fatty acids in seed triacylglycerols, however total seed oil is also reduced up to 50%. Investigations into the cause of the reduced oil phenotype through in vivo [14C]acteate and [3H]2O metabolic labeling of developing seeds surprisingly revealed that the rate of de novo fatty acid synthesis within the transgenic seeds was approximately half that of control seeds. Addition of castor phospholipid:diacylglycerol acyltransferase (PDAT) increased hydroxylated fatty acid content of the seed oil, increased the rate of fatty acid synthesis, and mostly restored seed oil levels. RNAseq analysis indicated no changes in expression of fatty acid synthesis genes in hydroxylase-expressing plants.
2014-01-10 | GSE53952 | GEO
Project description:Purkinje cells (PC) of the cerebellum degenerate in adult mice with mutations in the Niemann-Pick type C (NPC) disease 1 (Npc1) gene. We subjected BALB/c Npc1+/+ and Npc1-/- mouse cerebella from an early and a later time point of PC degeneration to a genome-wide microarray gene expression analysis. We found general underrepresentation of PC-specific transcripts, consistent with PC loss, and elevated markers of microglia activation at the later time point. Keywords: Niemann-Pick type C, Purkinje cell degeneration
2007-07-01 | GSE5944 | GEO
Project description:Fatty acids comprise the primary energy source for the heart and are mainly taken up via hydrolysis of circulating triglyceride-rich lipoproteins. While most of the fatty acids entering the cardiomyocyte are oxidized, a small portion is involved in altering gene transcription to modulate cardiometabolic functions. So far, no in vivo model has been developed enabling study of the transcriptional effects of specific fatty acids in the intact heart. In the present study, mice were given a single oral dose of synthetic triglycerides composed of one single fatty acid. Hearts were collected 6h thereafter and used for whole genome gene expression profiling. Experiments were conducted in wild-type and PPARalpha-/- mice to allow exploration of the specific contribution of PPARalpha. It was found that: 1) linolenic acid (C18:3) had the most pronounced effect on cardiac gene expression. 2) The largest similarity in gene regulation was observed between linoleic acid (C18:2) and C18:3. Large similarity was also observed between the synthetic PPARalpha agonist Wy14643 and docosahexaenoic acid (C22:6). 3) Many genes were regulated by one particular treatment only. Genes regulated by one particular treatment showed large functional divergence. 4) The majority of genes responding to fatty acid treatment were regulated in a PPARalpha-dependent manner, emphasizing the importance of PPARalpha in mediating transcriptional regulation by fatty acids in the heart. 5) Several genes were robustly regulated by all or many of the fatty acids studied, mostly representing well-described targets of PPARs (e.g. Acot1, Angptl4, Ucp3). 6) Deletion and activation of PPARalpha had a major effect on expression of numerous genes involved in metabolism and immunity. Our analysis demonstrates the marked impact of dietary fatty acids on gene regulation in the heart via PPARalpha. To study the transcriptional effects of specific fatty acids in the intact heart, wild type and PPARalpha-/- mice were given a single oral dose of 4 synthetic triglycerides composed of one single fatty acid, as well as of the synthetic PPARalpha agonist Wy14,643. Hearts were collected 6h after gavag and used for whole genome gene expression profiling.
2012-02-21 | E-GEOD-30495 | biostudies-arrayexpress
Project description:Niemann-Pick type C (NPC) disease is a rare neurodegenerative disorder mainly caused by autosomal recessive mutations in Npc1 which result in abnormal late endosomal/lysosomal lipid storage. Although microgliosis is one of the prominent pathological features, consequences of NPC1 loss on microglial function and disease outcome remain largely unknown. Here, we provide an in-depth characterization of microglial proteomic signatures and phenotypes in an NPC1-deficient (Npc1-/-) murine model. We demonstrate that microglial defects, including enhanced phagocytosis and impaired lipid trafficking, occur early in the NPC pathological cascade and precede neuronal death. Compromised microglial function during Npc1-/- mouse development is reflected by enhanced synaptic pruning and deficient turnover of myelin. Accumulation of the undigested myelin occurs mainly within multi-vesicular bodies (MVBs) of Npc1-/- microglia and not within lysosomes. This is in agreement with the impairments in recycling of myelin into lipid droplets. Macrophages of NPC patients displayed similar molecular and functional alterations as murine Npc1-/- microglia, strengthening the role of NPC1 in immune homeostasis. Generated ex vivo assays using patient macrophages are novel promising clinical tools to monitor the progression and therapeutic efficacy in NPC patients.
2021-02-09 | PXD019447 | Pride
Project description:Impacts of different fatty acids on the gut microbiota in the murine model of postmenopause
| PRJEB59939 | ENA
Project description:Acute effects of different dietary fatty acids on the gene expression profiles of peripheral blood mononuclear cells in healthy young men. A randomized cross-over study.
2009-11-01 | E-MTAB-65 | biostudies-arrayexpress