Perinatal Dietary Polyunsaturated Fatty Acids in Brain Development, Role in Neurodevelopmental Disorders.
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ABSTRACT:
SUBMITTER: Martinat M
PROVIDER: S-EPMC8065891 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Rats were fed either a high linolenic acid (perilla oil) or high eicosapentaenoic + docosahexaenoic acid (fish oil) diet (8%), and the fatty acid and molecular species composition of ethanolamine phosphoglycerides was determined. Gene expression pattern resulting from the feeding of n-3 fatty acids also was studied. Perilla oil feeding, in contrast to fish oil feeding, was not reflected in total fatty acid composition of ethanolamine phosphoglycerides. Levels of the alkenylacyl subclass of ethanolamine phosphoglycerides increased in response to feeding. Similarly, levels of diacyl phosphatidylethanolamine molecular species containing docosahexaenoic acid (18:0/22:6) were higher in perilla-fed or fish oil-fed rat brains whereas those in ethanolamine plasmalogens remained unchanged. Because plasmalogen levels in the brains of rats fed a n-3 fatty acid-enriched diet increased, it is plausible, however, that docosahexaenoic acid taken up from the food or formed from linolenic acid was deposited in this phospholipid subclass. Using cDNA microarrays, 55 genes were found to be overexpressed and 47 were suppressed relative to controls by both dietary regimens. The altered genes included those controlling synaptic plasticity, cytosceleton and membrane association, signal transduction, ion channel formation, energy metabolism, and regulatory proteins. This effect seems to be independent of the chain length of fatty acids, but the n-3 structure appears to be important. Because n-3 polyunsaturated fatty acids have been shown to play an important role in maintaining normal mental functions and docosahexaenoic acid-containing ethanolamine phosphoglyceride (18:0/22:6) molecular species accumulated in response to n-3 fatty acid feeding, a casual relationship between the two events can be surmised.
| S-EPMC122397 | biostudies-literature
Project description:The current report provides a brief background introducing 30 years of research on long-chain polyunsaturated fatty acids (LC-PUFA) and infant development, but focuses mainly on challenges for future studies. Infants fed formulas containing only vegetable fats were found to have lower docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (20:4n-6) status than infants fed human milk. Studies soon focused on efforts to improve LC-PUFA status and evaluate functions suggested by early primate studies of DHA deficiency. Despite evidence for the importance of these fatty acids for development, particularly DHA, several recent meta-analyses conclude dietary supplementation does not enhance development. Future studies should employ (1) more finely grained measures of brain development as opposed to global measures, and (2) tests that evaluate development later in childhood when children are able to be tested on more complex behaviors (if found effective these would also be evidence of early brain programming). (3) Studies are needed to understand the cause of high variability in transfer of DHA to the fetus. (4) Finally, the role of single-nucleotide polymorphisms of the fatty acid desaturase genes 1 and 2 of mother and infant needs study to determine how they affect requirements for these fatty acids by the fetus/infant.
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Project description:The neural tissue is rich in polyunsaturated fatty acids (PUFAs), components that are indispensable for the proper functioning of neurons, such as neurotransmission. PUFA nutritional deficiency and imbalance have been linked to a variety of chronic brain disorders, including major depressive disorder (MDD), anxiety, and anorexia. However, the effects of PUFAs on brain disorders remain inconclusive, and the extent of their shared genetic determinants is largely unknown. Here, we used genome-wide association summary statistics to systematically examine the shared genetic basis between six phenotypes of circulating PUFAs (N = 114,999) and 20 brain disorders (N = 9,725-762,917), infer their potential causal relationships, identify colocalized regions, and pinpoint shared genetic variants. Genetic correlation and polygenic overlap analyses revealed a widespread shared genetic basis for 77 trait pairs between six PUFA phenotypes and 16 brain disorders. Two-sample Mendelian randomization analysis indicated potential causal relationships for 16 pairs of PUFAs and brain disorders, including alcohol consumption, bipolar disorder (BIP), and MDD. Colocalization analysis identified 40 shared loci (13 unique) among six PUFAs and ten brain disorders. Twenty-two unique variants were statistically inferred as candidate shared causal variants, including rs1260326 (GCKR), rs174564 (FADS2) and rs4818766 (ADARB1). These findings reveal a widespread shared genetic basis between PUFAs and brain disorders, pinpoint specific shared variants, and provide support for the potential effects of PUFAs on certain brain disorders, especially MDD, BIP, and alcohol consumption.
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Project description:Ornithine decarboxylase 1 (ODC1 gene) has been linked through gain-of-function variants to a rare disease featuring developmental delay, alopecia, macrocephaly, and structural brain anomalies. ODC1 has been linked to additional diseases like cancer, with growing evidence for neurological contributions to schizophrenia, mood disorders, anxiety, epilepsy, learning, and suicidal behavior. The evidence of ODC1 connection to neural disorders highlights the need for a systematic analysis of ODC1 genotype-to-phenotype associations. An analysis of variants from ClinVar, Geno2MP, TOPMed, gnomAD, and COSMIC revealed an intellectual disability and seizure connected loss-of-function variant, ODC G84R (rs138359527, NC_000002.12:g.10444500C > T). The missense variant is found in ~1% of South Asian individuals and results in 2.5-fold decrease in enzyme function. Expression quantitative trait loci (eQTLs) reveal multiple functionally annotated, non-coding variants regulating ODC1 that associate with psychiatric/neurological phenotypes. Further dissection of RNA-Seq during fetal brain development and within cerebral organoids showed an association of ODC1 expression with cell proliferation of neural progenitor cells, suggesting gain-of-function variants with neural over-proliferation and loss-of-function variants with neural depletion. The linkage from the expression data of ODC1 in early neural progenitor proliferation to phenotypes of neurodevelopmental delay and to the connection of polyamine metabolites in brain function establish ODC1 as a bona fide neurodevelopmental disorder gene.
| S-EPMC8064465 | biostudies-literature
Project description:Dietary fat subtypes may play an important role in the regulation of muscle mass and function during ageing. The aim of the present study was to determine the impact of isocaloric macronutrient substitutions, including different fat subtypes, on sarcopenia risk in older men and women, while accounting for physical activity (PA) and metabolic risk. A total of 986 participants, aged 65-79 years, completed a 7-day food record and wore an accelerometer for a week. A continuous sex-specific sarcopenia risk score (SRS), including skeletal muscle mass assessed by dual-energy X-ray absorptiometry (DXA) and handgrip strength, was derived. The impact of the isocaloric replacement of saturated fatty acids (SFAs) by either mono- (MUFAs) or poly-unsaturated (PUFAs) fatty acids on SRS was determined using regression analysis based on the whole sample and stratified by adherence to a recommended protein intake (1.1 g/BW). Isocaloric reduction of SFAs for the benefit of PUFAs was associated with a lower SRS in the whole population, and in those with a protein intake below 1.1 g/BW, after accounting for age, smoking habits, metabolic disturbances, and adherence to PA guidelines. The present study highlighted the potential of promoting healthy diets with optimised fat subtype distribution in the prevention of sarcopenia in older adults.
| S-EPMC7600824 | biostudies-literature
Project description:N-3 polyunsaturated fatty acids (PUFAs) are essential nutrients that must be obtained from the diet. We have previously showed that endogenous n-3 PUFAs contribute to skeletal development and bone quality in fat-1 mice. Unlike other mammals, these transgenic mice, carry the n-3 desaturase gene and thus can convert n-6 to n-3 PUFAs endogenously. Since this model does not mimic dietary exposure to n-3 PUFAs, diets rich in fish and flaxseed oils were used to further elucidate the role of n-3 PUFAs in bone development. Our investigation reveals that dietary n-3 PUFAs decrease fat accumulation in the liver, lower serum fat levels, and alter fatty acid (FA) content in liver and serum. Bone analyses show that n-3 PUFAs improve mechanical properties, which were measured using a three-point bending test, but exert complex effects on bone structure that vary according to its source. In a micro-CT analysis, we found that the flaxseed oil diet improves trabecular bone micro-architecture, whereas the fish oil diet promotes higher bone mineral density (BMD) with no effect on trabecular bone. The transcriptome characterization of bone by RNA-seq identified regulatory mechanisms of n-3 PUFAs via modulation of the cell cycle and peripheral circadian rhythm genes. These results extend our knowledge and provide insights into the molecular mechanisms of bone remodeling regulation induced by different sources of dietary n-3 PUFAs.
| S-EPMC7697266 | biostudies-literature
Project description:Perinatal exposure to omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can be characterized through biomarkers in maternal or cord blood or breast milk. Objectives were to describe perinatal PUFA status combining multiple biofluids and to investigate how it was influenced by dietary intake during pregnancy and maternal FADS and ELOVL gene polymorphisms. This study involved 1,901 mother-child pairs from the EDEN cohort, with PUFA levels measured in maternal and cord erythrocytes, and colostrum. Maternal dietary PUFA intake during the last trimester was derived from a food frequency questionnaire. Twelve single-nucleotide polymorphisms in FADS and ELOVL genes were genotyped from maternal DNA. Principal component analysis incorporating PUFA levels from the three biofluids identified patterns of perinatal PUFA status. Spearman's correlations explored associations between patterns and PUFA dietary intake, and linear regression models examined pattern associations with FADS or ELOVL haplotypes. Five patterns were retained: "High omega-3 LC-PUFAs, low omega-6 LC-PUFAs"; "Omega-6 LC-PUFAs"; "Colostrum LC-PUFAs"; "Omega-6 precursor (LA) and DGLA"; "Omega-6 precursor and colostrum ALA". Maternal omega-3 LC-PUFA intakes were correlated with "High omega-3 LC-PUFAs, low omega-6 LC-PUFAs" (r(DHA) = 0.33) and "Omega-6 LC-PUFAs" (r(DHA) = -0.19) patterns. Strong associations were found between FADS haplotypes and PUFA patterns except for "High omega-3 LC-PUFAs, low omega-6 LC-PUFAs". Lack of genetic association with the "High omega-3 LC-PUFAs, low omega-6 LC-PUFAs" pattern, highly correlated with maternal omega-3 LC-PUFA intake, emphasizes the importance of adequate omega-3 LC-PUFA intake during pregnancy and lactation. This study offers a more comprehensive assessment of perinatal PUFA status and its determinants.
| S-EPMC11231547 | biostudies-literature
Project description:Recent evidence has suggested that dietary polyunsaturated fatty acids (PUFAs) modulate inflammation; however, few studies have focused on the pathobiology of PUFA using isocaloric and isolipidic diets and it is unclear if the associated pathologies are due to dietary PUFA composition, lipid metabolism or obesity, as most studies compare diets fed ad libitum. Our studies used isocaloric and isolipidic liquid diets (35% of calories from fat), with differing compositions of omega (?)-6 or long chain (Lc) ?-3 PUFA that were pair-fed and assessed hepatic pathology, inflammation and lipid metabolism. Consistent with an isocaloric, pair-fed model we observed no significant difference in diet consumption between the groups. In contrast, the body and liver weight, total lipid level and abdominal fat deposits were significantly higher in mice fed an ?-6 diet. An analysis of the fatty acid profile in plasma and liver showed that mice on the ?-6 diet had significantly more arachidonic acid (AA) in the plasma and liver, whereas, in these mice ?-3 fatty acids such as eicosapentaenoic acid (EPA) were not detected and docosahexaenoic acid (DHA) was significantly lower. Histopathologic analyses documented that mice on the ?-6 diet had a significant increase in macrovesicular steatosis, extramedullary myelopoiesis (EMM), apoptotic hepatocytes and decreased glycogen storage in lobular hepatocytes, and hepatocyte proliferation relative to mice fed the Lc ?-3 diet. Together, these results support PUFA dietary regulation of hepatic pathology and inflammation with implications for enteral feeding regulation of steatosis and other hepatic lesions.
| S-EPMC5996979 | biostudies-literature
Project description:The health benefits of diets containing rich sources of long-chain omega-3 polyunsaturated fatty acids (n-3 LC-PUFA) are well documented and include reductions in the risk of several diseases typical of Western societies. The dietary intake of n-3 LC-PUFA has also been linked to fertility, and there is abundant evidence that a range of ejaculate traits linked to fertility in humans, livestock and other animals depend on an adequate intake of n-3 LC-PUFA from dietary sources. However, relatively few studies have explored how n-3 LC-PUFA influence reproductive fitness, particularly in the context of sexual selection. Here, we show that experimental reduction in the level of n-3 LC-PUFA in the diet of guppies (Poecilia reticulata) depresses a male's share of paternity when sperm compete for fertilization, confirming that the currently observed trend for reduced n-3 LC-PUFA in western diets has important implications for individual reproductive fitness.
| S-EPMC4190967 | biostudies-literature
Project description:Aging contributes to physiological decline and vulnerability to disease. In the brain, even with minimal neuronal loss, aging increases oxidative damage, inflammation, demyelination, impaired processing, and metabolic deficits, particularly during pathological brain aging. In this review, the possible role of docosahexaenoic acid (DHA) in the prevention of age-related disruption of brain function is discussed. High-fat diabetogenic diets, cholesterol, and the omega-6 fatty acid arachidonate and its prostaglandin metabolites have all been implicated in promoting the pathogenesis of Alzheimer's disease. Evidence presented here shows DHA acts to oppose this, exerting a plethora of pleiotropic activities to protect against the pathogenesis of Alzheimer's disease.
| S-EPMC4019000 | biostudies-literature