Does polymorphisms in PPAR and APOE genes modify associations between fatty acid desaturase (FADS), n-3 long-chain PUFA and cardiometabolic markers in 8–11-year-old Danish children?

2020 ◽  
pp. 1-8
Author(s):  
Camilla T. Damsgaard ◽  
Stine Vuholm ◽  
Marie N. Teisen ◽  
Ken D. Stark ◽  
Lotte Lauritzen
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Desaturase ◽  
Hdl Cholesterol ◽  
Blood Cholesterol ◽  
Dependent Manner ◽  
Chain Pufa ◽  
Major Allele ◽  
Cardiometabolic Markers ◽  
Cardiometabolic Profile ◽  
Long Chain

Abstract n-3 Long-chain PUFA (LCPUFA) can improve cardiometabolic blood markers, but studies in children are limited. SNP in the FADS genes, which encode fatty acid desaturases, influence endogenous LCPUFA production. Moreover, SNP in genes that encode PPAR and apoE may modulate the effects of n-3 LCPUFA. We explored whether FADS polymorphisms were associated with blood cholesterol and TAG, insulin and glucose and whether polymorphisms in PPAR and APOE modified associations between FADS or n-3 LCPUFA status and the cardiometabolic blood markers. We measured fasting cholesterol and TAG, insulin, glucose and n-3 LCPUFA in 757 Danish 8–11-year-old children and genotyped SNP in FADS (rs1535 and rs174448), PPARG2 (rs1801282), PPARA (rs1800206) and APOE (rs7412+rs429358). Carriage of two FADS rs174448 major alleles was associated with lower TAG (P = 0·027) and higher HDL-cholesterol (P = 0·047). Blood n-3 LCPUFA was inversely associated with TAG and insulin in PPARG2 minor allele carriers and positively with LDL-cholesterol in major allele homozygotes (Pn-3 LCPUFA × rs180182 < 0·01). Associations between n-3 LCPUFA and cardiometabolic markers were not modified by APOE genotype (Pn-3 LCPUFA × APOE > 0·11), but interaction between FADS rs1535 and APOE showed that rs1535 major allele homozygotes who also carried APOE2 had higher HDL-cholesterol than all other genotype combinations (Prs1535 × APOE = 0·019, pairwise-P < 0·05). This indicates that FADS genotypes, which increase endogenous LCPUFA production, may beneficially affect children’s cardiometabolic profile in a partly APOE-dependent manner. Also, the degree to which children benefit from higher n-3 LCPUFA intake may depend on their PPARG2 genotype.

scholarly journals Maternal and child fatty acid desaturase genotype as determinants of cord blood long-chain PUFA (LCPUFA) concentrations in the Seychelles Child Development Study

2021 ◽  
pp. 1-11
Author(s):  
Marie C. Conway ◽  
Emeir M. McSorley ◽  
Maria S. Mulhern ◽  
Toni Spence ◽  
Maria Weslowska ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Child Development ◽  
Cord Blood ◽  
Fatty Acid Desaturase ◽  
Minor Allele ◽  
Total Serum ◽  
Development Study ◽  
Blood Concentrations ◽  
Chain Pufa ◽  
Long Chain

Abstract Optimal maternal long-chain PUFA (LCPUFA) status is essential for the developing fetus. The fatty acid desaturase (FADS) genes are involved in the endogenous synthesis of LCPUFA. The minor allele of various FADS SNP have been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of arachidonic acid (AA) and DHA. There is limited research on the influence of FADS genotype on cord PUFA status. The current study investigated the influence of maternal and child genetic variation in FADS genotype on cord blood PUFA status in a high fish-eating cohort. Cord blood samples (n 1088) collected from the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Of those with cord PUFA data available, maternal (n 1062) and child (n 916), FADS1 (rs174537 and rs174561), FADS2 (rs174575), and FADS1-FADS2 (rs3834458) were determined. Regression analysis determined that maternal minor allele homozygosity was associated with lower cord blood concentrations of DHA and the sum of EPA + DHA. Lower cord blood AA concentrations were observed in children who were minor allele homozygous for rs3834458 (β = 0·075; P = 0·037). Children who were minor allele carriers for rs174537, rs174561, rs174575 and rs3834458 had a lower cord blood AA:LA ratio (P < 0·05 for all). Both maternal and child FADS genotype were associated with cord LCPUFA concentrations, and therefore, the influence of FADS genotype was observed despite the high intake of preformed dietary LCPUFA from fish in this population.

scholarly journals The compositional and metabolic responses of gilthead seabream (Sparus aurata) to a gradient of dietary fish oil and associatedn-3 long-chain PUFA content

2017 ◽  
Vol 118 (12) ◽  
pp. 1010-1022 ◽  
Author(s):  
Sam J. S. Houston ◽  
Vasileios Karalazos ◽  
John Tinsley ◽  
Mónica B. Betancor ◽  
Samuel A. M. Martin ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fish Oil ◽  
Fatty Acid Synthase ◽  
Sparus Aurata ◽  
Gilthead Seabream ◽  
Dependent Manner ◽  
Tissue Fatty Acid ◽  
Chain Pufa ◽  
Fat Deposits ◽  
Long Chain

AbstractThe replacement of fish oil (FO) with vegetable oil (VO) in feed formulations reduces the availability ofn-3 long-chain PUFA (LC-PUFA) to marine fish such as gilthead seabream. The aim of this study was to examine compositional and physiological responses to a dietary gradient ofn-3 LC-PUFA. Six iso-energetic and iso-nitrogenous diets (D1–D6) were fed to seabream, with the added oil being a blend of FO and VO to achieve a dietary gradient ofn-3 LC-PUFA. Fish were sampled after 4 months feeding, to determine biochemical composition, tissue fatty acid concentrations and lipid metabolic gene expression. The results indicated a disturbance to lipid metabolism, with fat in the liver increased and fat deposits in the viscera reduced. Tissue fatty acid profiles were altered towards the fatty acid compositions of the diets. There was evidence of endogenous modification of dietary PUFA in the liver which correlated with the expression of fatty acid desaturase 2 (fads2). Expression of sterol regulatory element binding protein 1 (srebp1), fads2and fatty acid synthase increased in the liver, whereas PPARα1 pathways appeared to be supressed by dietary VO in a concentration-dependent manner. The effects in lipogenic genes appear to become measurable in D1–D3, which agrees with the weight gain data suggesting that disturbances to energy metabolism and lipogenesis may be related to performance differences. These findings suggested that suppression ofβ-oxidation and stimulation ofsrebp1-mediated lipogenesis may play a role in contributing toward steatosis in fish fedn-3 LC-PUFA deficient diets.

scholarly journals Unique fatty acid desaturase capacities uncovered in Hediste diversicolor illustrate the roles of aquatic invertebrates in trophic upgrading

2020 ◽  
Vol 375 (1804) ◽  
pp. 20190654 ◽  
Author(s):  
Naoki Kabeya ◽  
İbrahim Gür ◽  
Angela Oboh ◽  
Jan Ove Evjemo ◽  
Arne M. Malzahn ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Aquatic Invertebrates ◽  
Fatty Acid Desaturase ◽  
Benthic Fauna ◽  
Dietary Fatty Acids ◽  
Omega 3 ◽  
Hediste Diversicolor ◽  
Chain Pufa ◽  
Long Chain

Omega-3 ( ω 3 or n -3) long-chain polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid and docosahexaenoic acid (DHA), play physiologically important roles in vertebrates. These compounds have long been believed to have originated almost exclusively from aquatic (mostly marine) single-cell organisms. Yet, a recent study has discovered that many invertebrates possess a type of enzymes called methyl-end desaturases ( ω x ) that enables them to endogenously produce n -3 long-chain PUFA and could make a significant contribution to production of these compounds in the marine environment. Polychaetes are major components of benthic fauna and thus important to maintain a robust food web as a recycler of organic matter and a prey item for higher trophic level species like fish. In the present study, we investigated the ω x enzymes from the common ragworm, Hediste diversicolor , a common inhabitant in sedimentary littoral ecosystems of the North Atlantic. Functional assays of the H. diversicolor ω x demonstrated unique desaturation capacities. An ω 3 desaturase mediated the conversion of n -6 fatty acid substrates into their corresponding n -3 products including DHA. A further enzyme possessed unique regioselectivities combining both ω 6 and ω 3 desaturase activities. These results illustrate that the long-chain PUFA biosynthetic enzymatic machinery of aquatic invertebrates such as polychaetes is highly diverse and clarify that invertebrates can be major contributors to fatty acid trophic upgrading in aquatic food webs. This article is part of the theme issue ‘The next horizons for lipids as ‘trophic biomarkers’: evidence and significance of consumer modification of dietary fatty acids’.

scholarly journals Identification of Fatty Acid Desaturase 6 in Golden Pompano Trachinotus Ovatus (Linnaeus 1758) and Its Regulation by the PPARαb Transcription Factor

2018 ◽  
Vol 20 (1) ◽  
pp. 23 ◽  
Author(s):  
Ke-Cheng Zhu ◽  
Ling Song ◽  
Hua-Yang Guo ◽  
Liang Guo ◽  
Nan Zhang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Fatty Acid ◽  
Binding Site ◽  
Functional Characterization ◽  
Fatty Acid Desaturase ◽  
Chain Polyunsaturated Fatty Acid ◽  
Dependent Manner ◽  
Fatty Acid Desaturases ◽  
Trachinotus Ovatus ◽  
Long Chain

Fatty acid desaturases are rate-limiting enzymes in long-chain polyunsaturated fatty acid biosynthesis. The transcription factor peroxisome proliferator-activated receptor alpha b (PPARαb) regulates lipid metabolism in mammals, however, the mechanism whereby PPARαb regulates fatty acid desaturases is largely unknown in fish. In this study, we report the full length cDNA sequence of Trachinotus ovatus fatty acid desaturase, which encodes a 380 amino acid polypeptide, possessing three characteristic histidine domains. Phylogenetic and gene exon/intron structure analyses showed typical phylogeny: the T. ovatus fatty acid desaturase contained a highly conserved exon/intron architecture. Moreover, functional characterization by heterologous expression in yeast indicated that T. ovatus desaturase was a fatty acid desaturase, with Δ4/Δ5/Δ8 Fad activity. Promoter activity assays indicated that ToFads6 desaturase transcription was positively regulated by PPARαb. Similarly, PPARαb RNA interference decreased ToPPARαb and ToFads6 expression at the mRNA and protein levels in a time-dependent manner. Mutation analyses showed that the M2 binding site of PPARαb was functionally important for protein binding, and transcriptional activity of the ToFads6 promoter was significantly decreased after targeted mutation of M2. Electrophoretic mobile shift assays confirmed that PPARαb interacted with the binding site of the ToFads6 promoter region, to regulate ToFads6 transcription. In summary, PPARαb played a vital role in ToFads6 regulation and may promote the biosynthesis of long-chain polyunsaturated fatty acids by regulating ToFads6 expression.

scholarly journals The Source of Long-Chain PUFA in Formula Supplements Does Not Affect the Fatty Acid Composition of Plasma Lipids in Full-Term Infants

2004 ◽  
Vol 134 (4) ◽  
pp. 868-873 ◽  
Author(s):  
Aleix Sala-Vila ◽  
Ana I. Castellote ◽  
Cristina Campoy ◽  
Montserrat Rivero ◽  
María Rodriguez-Palmero ◽  
...  
Keyword(s):  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Acid Composition ◽  
Plasma Lipids ◽  
Full Term ◽  
Term Infants ◽  
Chain Pufa ◽  
Long Chain

scholarly journals Dietary polyunsaturated fatty acids influence flight muscle oxidative capacity but not endurance flight performance in a migratory songbird

2019 ◽  
Vol 316 (4) ◽  
pp. R362-R375 ◽  
Author(s):  
Morag F. Dick ◽  
Christopher G. Guglielmo
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Empirical Evidence ◽  
Flight Muscle ◽  
Muscle Metabolism ◽  
Oxidative Enzymes ◽  
Flight Performance ◽  
Chain Pufa ◽  
Long Chain

The migratory flights of birds are primarily fueled by fat; however, certain fatty acids may also enhance flight performance and the capacity to oxidize fat. The natural doping hypothesis posits that n–3 long-chain polyunsaturated fatty acids (PUFA) increase membrane fluidity and aerobic and fatty acid oxidative enzymes in the flight muscles, which enables prolonged endurance flight. Support for this hypothesis is mixed, and there is no empirical evidence for increased flight performance. We fed yellow-rumped warblers ( Setophaga coronata coronata) diets enriched in either n–3 or n–6 long-chain PUFA or low in long-chain PUFA and evaluated flight muscle metabolism and endurance performance in a wind tunnel flights lasting up to 6 h. Fatty acid profiles of muscle phospholipids confirmed enrichment of the targeted dietary fatty acids, whereas less substantial differences were observed in adipose triacylglycerol. Contrary to the predictions, feeding n–3 PUFA decreased peroxisome proliferator-activated receptors-β mRNA abundance and muscle oxidative enzyme activities. However, changes in muscle metabolism were not reflected in whole animal performance. No differences were observed in flight performance among diet treatments in terms of endurance capacity, energy costs, or fuel composition. These measures of flight performance were more strongly influenced by body mass and flight duration. Overall, we found no support for the natural doping hypothesis in a songbird. Furthermore, we caution against extending changes in flight muscle metabolic enzymes or fatty acid composition to changes to migratory performance without empirical evidence.

scholarly journals Early nutrition in combination with polymorphisms in fatty acid desaturase gene cluster modulate fatty acid composition of cheek cells’ glycerophospholipids in school-age children

2019 ◽  
Vol 122 (s1) ◽  
pp. S68-S79
Author(s):  
Cristina Martínez-Zaldívar ◽  
Hatim Azaryah ◽  
José A. García-Santos ◽  
Hans Demmelmair ◽  
Signe Altmäe ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Gene Cluster ◽  
Mixed Model ◽  
Fatty Acid Desaturase ◽  
Docosapentaenoic Acid ◽  
School Age Children ◽  
Blood Levels ◽  
School Age ◽  
Early Nutrition ◽  
Chain Pufa

AbstractVariants in the human genes of fatty acid (FA) desaturase 1 (FADS1), 2 (FADS2) and 3 (FADS3) are associated with PUFA blood levels. We explored if maternal prenatal supplementation and children’s genetic variation in seventeen SNP of the FADS1, FADS2 and FADS3 gene cluster influence twenty-one of the most relevant cheek cells’ derived FA in glycerophospholipids (GPL-FA). The study was conducted in 147 Spanish and German mother–children pairs participating in the Nutraceuticals for a Healthier Life (NUHEAL) study at 8, 9 and 9·5 years. Linear and mixed model longitudinal regression analyses were performed. Maternal fish-oil (FO) or FO+5-methyltetrahydrofolate (5-MTHF) supplementation during pregnancy was associated with a significant decrease of arachidonic acid (AA) concentrations in cheek cell GPL in the offspring, from 8 to 9·5 years; furthermore, maternal FO+5-MTHF supplementation was associated with higher n-6 docosapentaenoic acid concentrations in their children at age 8 years. FADS1 rs174556 polymorphism and different FADS2 genotypes were associated with higher concentrations of linoleic and α-linolenic acids in children; moreover, some FADS2 genotypes determined lower AA concentrations in children’s cheek cells. It is suggested an interaction between type of prenatal supplementation and the offspring genetic background driving GPL-FA levels at school age. Prenatal FO supplementation, and/or with 5-MTHF, seems to stimulate n-3 and n-6 FA desaturation in the offspring, increasing long-chain PUFA concentrations at school age, but depending on children’s FADS1 and FADS2 genotypes. These findings suggest potential early nutrition programming of FA metabolic pathways, but interacting with children’s FADS polymorphisms.

Association between FADS1 rs174547 and levels of long-chain polyunsaturated fatty acids: a meta-analysis

2020 ◽  
pp. 1-26
Author(s):  
Yan Wang ◽  
Yiwei Tang ◽  
Ye Ji ◽  
Wenhui Xu ◽  
Naeem Ullah ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Meta Analysis ◽  
Fatty Acid Desaturase ◽  
Chain Polyunsaturated Fatty Acid ◽  
Single Nucleotide ◽  
Genotype Group ◽  
Asian Populations ◽  
Long Chain

Abstract In this study, we analysed the effects of single nucleotide polymorphism (SNP) rs174547 (T/C) in the fatty acid desaturase 1 (FADS1) gene on long-chain polyunsaturated fatty acid levels. Four databases were searched to retrieve related literature with keywords such as fatty acid, SNP, FADS1, and rs174547. A meta-analysis of the data was performed using Stata12.0 software, including summary statistics, test for heterogeneity, evaluation of publication bias, subgroup analysis, and sensitivity analysis. The associations between rs174547 in FADS1 and seven types of fatty acids, and delta-5 (D5D) and delta-6 fatty acid desaturase (D6D) activity were assessed based on the pooled results from 11 manuscripts. A total of 3713 individuals (1529 TT and 2184 TC+CC) were included. The results demonstrated that minor C allele carriers of rs174547 had higher linoleic acid (LA; P < 0.001) and α-linolenic acid (P = 0.020) levels, lower gamma linoleic acid (GLA; P = 0.001) and arachidonic acid (P = 0.024) levels, and lower D5D (P = 0.005) and D6D (P = 0.004) activities than the TT genotype group. Stratification analysis showed that minor C allele carriers of rs174547 had higher LA and lower GLA levels and lower D6D activities in plasma (LA, P < 0.001; GLA, P < 0.001; D6D activity, P < 0.001) samples and in Asian populations (LA, P < 0.001; GLA, P = 0.001; D6D activity, P = 0.001) than the TT genotype group. In conclusion, minor C allele carriers of the SNP rs174547 were associated with decreased activity of D5D and D6D.

scholarly journals Erythrocyte DHA level as a biomarker of DHA status in specific brain regions of n-3 long-chain PUFA-supplemented aged rats

2014 ◽  
Vol 112 (11) ◽  
pp. 1805-1818 ◽  
Author(s):  
Anne Létondor ◽  
Benjamin Buaud ◽  
Carole Vaysse ◽  
Laurence Fonseca ◽  
Coralie Herrouin ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Brain Regions ◽  
Erythrocyte Membranes ◽  
Aged Rats ◽  
Pufa Supplementation ◽  
Brain Functions ◽  
Chain Pufa ◽  
Brain Ageing ◽  
The Relationship ◽  
Long Chain

n-3 Long-chain PUFA (n-3 LC-PUFA), particularly EPA and DHA, play a key role in the maintenance of brain functions such as learning and memory that are impaired during ageing. Ageing is also associated with changes in the DHA content of brain membranes that could contribute to memory impairment. Limited studies have investigated the effects of ageing and n-3 LC-PUFA supplementation on both blood and brain fatty acid compositions. Therefore, we assessed the relationship between fatty acid contents in plasma and erythrocyte membranes and those in the hippocampus, striatum and cerebral cortex during ageing, and after a 5-month period of EPA/DHA supplementation in rats. In the blood, ageing was associated with an increase in plasma DHA content, whereas the DHA content remained stable in erythrocyte membranes. In the brain, ageing was associated with a decrease in DHA content, which was both region-specific and phospholipid class-specific. In EPA/DHA-supplemented aged rats, DHA contents were increased both in the blood and brain compared with the control rats. The present results demonstrated that n-3 LC-PUFA level in the plasma was not an accurate biomarker of brain DHA status during ageing. Moreover, we highlighted a positive relationship between the DHA levels in erythrocyte phosphatidylethanolamine (PE) and those in the hippocampus and prefrontal cortex in EPA/DHA-supplemented aged rats. Within the framework of preventive dietary supplementation to delay brain ageing, these results suggest the possibility of using erythrocyte PE DHA content as a reliable biomarker of DHA status in specific brain regions.

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