Efficacy and Safety of a PN Regimen Containing n-3 Fatty Acid in Patients Considered After GI Surgery
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ABSTRACT:
DISEASE(S): Gi Cancer
PROVIDER: 2064512 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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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: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: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: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.
2014-07-01 | GSE43642 | GEO
Project description:Metabolic diseases are closely linked to aberrant synthesis of endogenous fatty acids in the liver, called de novo lipogenesis (DNL), which is mediated by the enzyme fatty acid synthase (FASN). The composition of complex lipids consists of saturated or monosaturated fatty acids, which can be endogenously produced, and polyunsaturated fatty acids (PUFA), which are strictly dietary. Compositional differences between individuals are insufficiently understood and may influence the onset and progression of metabolic and cardiovascular diseases. Here we show that DNL critically determines the use of dietary PUFA. A patient with a hypofunctional heterozygous de novo Arg2177Cys variant in FASN exhibited an elevated composition of PUFA, which was phenocopied by pharmacological inhibition of FASN with TVB-2640 in patients with nonalcoholic steatohepatitis (NASH). In mice, the incorporation rate of supplemented omega-3 PUFA during an obesogenic diet was increased by genetic or pharmacologic reduction of DNL. Mechanistically, we show that the FASN variant exhibited a cysteine-dependent, non-enzymatic acetylation of FASN, which resulted in hyperubiquitinylation and decreased protein stability. Our study further reveals that PUFA storage is an active, enzymatic process controlled by FASN, diacylglycerol O-acyltransferase 2 (DGAT2) and MFSD2A, a membrane-transport protein, and that combining FASN inhibition and PUFA supplementation exerts additive beneficial metabolic effects. These findings provide evidence that the success of PUFA supplementation may depend on the rate of endogenous DNL and that combined PUFA supplementation and FASN inhibition may be a promising approach targeting metabolic disease.
2023-12-19 | PXD045908 | Pride
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: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: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.
2023-12-14 | E-MTAB-13399 | biostudies-arrayexpress
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. Abdominal subcutaneous adipose needle biopsies were obtained from young adults before (W0) and after completion (W7) of the dietary intervention. From the biopsies we extracted RNA. From total RNA we prepared and hybridised biotinylated complementary RNA to GeneChip Human Gene 1.1 ST Arrays (Affymetrix, Inc., Santa Clara, CA), and then washed, stained and scanned the slides using standardised protocols (Affymetrix, Inc.). Signicance analysis of microarrays (SAM) was use to compare the difference in gene expression between groups.
2014-07-01 | E-GEOD-43642 | biostudies-arrayexpress
Project description:Dietary fat quality may influence skeletal muscle lipid handling and fat accumulation, thereby modulating insulin sensitivity. Objective: To examine acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA handling and postprandial insulin sensitivity in obese insulin resistant men. Design: In a single-blinded randomized crossover study, 10 insulin resistant men consumed three high-fat mixed-meals (2.6MJ). Meals were high in saturated FA (SFA), in monounsaturated FA (MUFA) or in polyunsaturated FA (PUFA). Fasting and postprandial skeletal muscle FA handling were examined by measuring arterio-venous concentration differences across forearm muscle. [2H2]-palmitate was infused intravenously to label endogenous triacylglycerol (TAG) and FFA in the circulation and [U-13C]-palmitate was added to the meal to label chylomicron-TAG. Skeletal muscle biopsies were taken to assess intramuscular lipid metabolism and gene expression. Results: Insulin and glucose responses (AUC) after SFA meal were significantly higher compared with PUFA meal (p=0.003 and 0.028, respectively). Uptake of TAG-derived FA was significantly lower in the early postprandial phase after PUFA meal as compared with other meals (AUC60-120, p<0.001). The PUFA meal induced less transcriptional downregulation of oxidative pathways compared with other meals. The fractional synthetic rate was higher in DAG and PL fraction after MUFA and PUFA meal. Conclusion: Intake of a PUFA meal reduced TAG-derived skeletal muscle FA uptake, which was accompanied by higher postprandial insulin sensitivity and a tendency towards a higher muscle lipid turnover. These data suggest that the effects of replacement of SFA by PUFA may contribute to less muscle lipid uptake and may be therefore protective against the development of insulin resistance. Keywords: expression profiling by array randomized crossover dietary intervention study
2012-02-21 | E-GEOD-31901 | biostudies-arrayexpress