During pregnancy, maternal plasma fatty acids are critically required for cell growth and development, cell signaling, and the development of critical structural and functional aspects of the ...feto-placental unit. In addition, the fatty acids modulate the early stages of placental development by regulating angiogenesis in the first-trimester human placenta. Preferential transport of maternal plasma long-chain polyunsaturated fatty acids during the third trimester is critical for optimal fetal brain development. Maternal status such as obesity, diabetes, and dietary intakes may affect the functional changes in lipid metabolic processes in maternal-fetal lipid transport and metabolism. Fatty acids traverse the placental membranes
several plasma membrane fatty acid transport/binding proteins (FAT, FATP, p-FABPpm, and FFARs) and cytoplasmic fatty acid-binding proteins (FABPs). This review discusses the maternal metabolism of fatty acids and their effects on early placentation, placental fatty acid transport and metabolism, and their roles in feto-placental growth and development. The review also highlights how maternal fat metabolism modulates lipid processing, including transportation, esterification, and oxidation of fatty acids.
•Docosahexaenoic acid,22:6n-3 (DHA) is important for brain growth and development.•Dietary intake of DHA is recommended throughout the life cycle.•DHA and its metabolites are involved in the brain ...structure and function.•DHA deficiency is observed in brain disorders.•Clinical trials of DHA supplementation improve brain function.
Docosahexaenoic acid,22:6n-3 (DHA) and its metabolites are vital for the structure and functional brain development of the fetus and infants, and also for maintenance of healthy brain function of adults. DHA is thought to be an essential nutrient required throughout the life cycle for the maintenance of overall brain health. The mode of actions of DHA and its derivatives at both cellular and molecular levels in the brain are emerging. DHA is the major prevalent fatty acid in the brain membrane. The brain maintains its fatty acid levels mainly via the uptake of plasma free fatty acids. Therefore, circulating plasma DHA is significantly related to cognitive abilities during ageing and is inversely associated with cognitive decline. The signaling pathways of DHA and its metabolites are involved in neurogenesis, antinociceptive effects, anti‐apoptotic effect, synaptic plasticity, Ca2+ homeostasis in brain diseases, and the functioning of nigrostriatal activities. Mechanisms of action of DHA metabolites on various processes in the brain are not yet well known. Epidemiological studies support a link between low habitual intake of DHA and a higher risk of brain disorders. A diet characterized by higher intakes of foods containing high in n‐3 fatty acids, and/or lower intake of n‐6 fatty acids was strongly associated with a lower Alzheimer's Disease and other brain disorders. Supplementation of DHA improves some behaviors associated with attention deficit hyperactivity disorder, bipolar disorder, schizophrenia, and impulsive behavior, as well as cognition. Nevertheless, the outcomes of trials with DHA supplementation have been controversial. Many intervention studies with DHA have shown an apparent benefit in brain function. However, clinical trials are needed for definitive conclusions. Dietary deficiency of n‐3 fatty acids during fetal development in utero and the postnatal state has detrimental effects on cognitive abilities. Further research in humans is required to assess a variety of clinical outcomes, including quality of life and mental status, by supplementation of DHA.
Dietary components are essential for the structural and functional development of the brain. Among these, docosahexaenoic acid, 22:6n-3 (DHA), is critically necessary for the structure and ...development of the growing fetal brain
. DHA is the major n-3 long-chain polyunsaturated fatty acid in brain gray matter representing about 15% of all fatty acids in the human frontal cortex. DHA affects neurogenesis, neurotransmitter, synaptic plasticity and transmission, and signal transduction in the brain. Data from human and animal studies suggest that adequate levels of DHA in neural membranes are required for maturation of cortical astrocyte, neurovascular coupling, and glucose uptake and metabolism. Besides, some metabolites of DHA protect from oxidative tissue injury and stress in the brain. A low DHA level in the brain results in behavioral changes and is associated with learning difficulties and dementia. In humans, the third trimester-placental supply of maternal DHA to the growing fetus is critically important as the growing brain obligatory requires DHA during this window period. Besides, DHA is also involved in the early placentation process, essential for placental development. This underscores the importance of maternal intake of DHA for the structural and functional development of the brain. This review describes DHA's multiple roles during gestation, lactation, and the consequences of its lower intake during pregnancy and postnatally on the 2019 brain development and function.
•Inappropriate intakes of n-6 and n-3 fatty acids in pregnancy carry risks for the fetal development and diseases in later life.•In addition to deficit intakes of several dietary factors by mothers ...in India, n-3 deficiency seems to be the most prominent.•The n-3 deficiency affects fetal growing tissues globally such as the brain, motor nerve, muscle, eye, adiposity etc.•Maternal deficiency of n-3 fatty acids may also affect placental angiogenesis and thereby its structure and function.•Maternal intake of n-3 fatty acids must be followed with ISSFAL guidelines to improve maternal health and fetal development.
Polyunsaturated fatty acids (PUFAs) play multiple physiological roles. They regulate the structure and function of cell membranes and cell growth and proliferation, and apoptosis. In addition, PUFAs are involved in cellular signaling, gene expression and serve as precursors to second messengers such as eicosanoids, docosanoids etc. and regulate several physiological processes including placentation, inflammation, immunity, angiogenesis, platelet function, synaptic plasticity, neurogenesis, bone formation, energy homeostasis, pain sensitivity, stress, and cognitive functions. Linoleic acid, 18:2n-6 (LA) and alpha-linolenic acid, 18:3n-3 (ALA) are the two essential fatty acids obtained from the diets and subsequently their long-chain polyunsaturated fatty acids (LCPUFAs) are accumulated in the body. The maternal plasma LCPUFAs especially accumulated in larger amounts in the brain during the third trimester of pregnancy via the placenta and postnatally from mother's breast milk. Various studies, including ours, suggest PUFA's important role in placentation, as well as in growth and development of the offspring. However, intakes of maternal n-3 PUFAs during pregnancy and lactation are much lower in India compared with the Western population. In India, n-3 fatty acid status is further reduced by higher intake of n-6 PUFA rich oils and trans fats. More data on the impacts of long term maternal n-3 PUFA deficiency on placental structure and function, gene expression, epigenetic changes and resultant cognitive function of fetus & infants are emerging. This review summarizes the impacts of n-3 PUFA deficiency in utero on fetal growth and development, adiposity, energy metabolism, musculoskeletal development, and epigenetic changes in feto-placental axis from the recently available pre-clinical and clinical data.
During the last trimester of gestation and for the first 18 months after birth, both docosahexaenoic acid,22:6n-3 (DHA) and arachidonic acid,20:4n-6 (ARA) are preferentially deposited within the ...cerebral cortex at a rapid rate. Although the structural and functional roles of DHA in brain development are well investigated, similar roles of ARA are not well documented. The mode of action of these two fatty acids and their derivatives at different structural–functional roles and their levels in the gene expression and signaling pathways of the brain have been continuously emanating. In addition to DHA, the importance of ARA has been much discussed in recent years for fetal and postnatal brain development and the maternal supply of ARA and DHA. These fatty acids are also involved in various brain developmental processes; however, their mechanistic cross talks are not clearly known yet. This review describes the importance of ARA, in addition to DHA, in supporting the optimal brain development and growth and functional roles in the brain.
Daily exposure to bisphenols can affect reproductive functions due to their pseudo-estrogenic and/or anti-androgenic effects. Testicular lipids contain high levels of polyunsaturated fatty acids ...necessary for sperm maturity, motility, and spermatogenesis. Whether prenatal exposure to bisphenols alters testicular fatty acid metabolism in adult offspring is unknown. Pregnant Wistar rats were gavaged from gestational day 4 to 21 with BPA and BPS (0.0, 0.4, 4.0, 40.0 μg/kg bw/day). Despite increased body and testis weight, the total testicular cholesterol, triglyceride, and plasma fatty acids were unaffected in the offspring. Lipogenesis was upregulated by increased SCD-1, SCD-2, and expression of lipid storage (ADRP) and trafficking protein (FABP4). The arachidonic acid, 20:4 n-6 (ARA) and docosapentaenoic acid, 22:5 n-6 (DPA) levels were decreased in the BPA-exposed testis, while BPS exposure had no effects. The expression of PPARα, PPARγ proteins, and CATSPER2 mRNA were decreased, which are important for energy dissipation and the motility of the sperm in the testis. The endogenous conversion of linoleic acid,18:2 n-6 (LA), to ARA was impaired by a reduced ARA/LA ratio and decreased FADS1 expression in BPA-exposed testis. Collectively, fetal BPA exposure affected endogenous long-chain fatty acid metabolism and steroidogenesis in the adult testis, which might dysregulate sperm maturation and quality.
Maternal endocrine homeostasis is vital to a successful pregnancy, regulated by several hormones such as human chorionic gonadotropin, estrogen, leptin, glucocorticoid, insulin, prostaglandin, and ...others. Endocrine stress during pregnancy can modulate nutrient availability from mother to fetus, alter fetoplacental growth and reproductive functions. Endocrine disrupters such as bisphenols (BPs) and phthalates are exposed in our daily life's highest volume. Therefore, they are extensively scrutinized for their effects on metabolism, steroidogenesis, insulin signaling, and inflammation involving obesity, diabetes, and the reproductive system. BPs have their structural similarity to 17-β estradiol and their ability to bind as an agonist or antagonist to estrogen receptors to elicit an adverse response to the function of the endocrine and reproductive system. While adults can negate the adverse effects of these endocrine-disrupting chemicals (EDCs), fetuses do not equip themselves with enzymatic machinery to catabolize their conjugates. Therefore, EDC exposure makes the fetoplacental developmental window vulnerable to programming
in utero
. On the one hand prenatal BPs and phthalates exposure can impair the structure and function of the ovary and uterus, resulting in placental vascular defects, inappropriate placental expression of angiogenic growth factors due to altered hypothalamic response, expression of nutrient transporters, and epigenetic changes associated with maternal endocrine stress. On the other, their exposure during pregnancy can affect the offspring's metabolic, endocrine and reproductive functions by altering fetoplacental programming. This review highlights the latest development in maternal metabolic and endocrine modulations from exposure to estrogenic mimic chemicals on subcellular and transgenerational changes in placental development and its effects on fetal growth, size, and metabolic & reproductive functions.
Evidence is emerging on the role of maternal diet, gut microbiota, and other lifestyle factors in establishing lifelong health and disease, which are determined by transgenerationally inherited ...epigenetic modifications. Understanding epigenetic mechanisms may help identify novel biomarkers for gestation-related exposure, burden, or disease risk. Such biomarkers are essential for developing tools for the early detection of risk factors and exposure levels. It is necessary to establish an exposure threshold due to nutrient deficiencies or other environmental factors that can result in clinically relevant epigenetic alterations that modulate disease risks in the fetus. This narrative review summarizes the latest updates on the roles of maternal nutrients (n-3 fatty acids, polyphenols, vitamins) and gut microbiota on the placental epigenome and its impacts on fetal brain development. This review unravels the potential roles of the functional epigenome for targeted intervention to ensure optimal fetal brain development and its performance in later life.
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•Dietary fats, modulate metabolic syndrome and associated features.•Gut microbiota and their short-chain metabolites affect inflammation, lipid metabolism, and other features of ...metabolic syndrome.•The gut microbiota modulate host metabolism associated with inflammation, blood pressure, and predisposes risk of metabolic syndrome.
The metabolic syndrome (MetS) produces low-grade inflammation, endothelial dysfunction, platelet hyperactivity, oxidative stress and ultimately contributes to cardiovascular disease (CVD) development. Fatty acids such as n-3 and n-6, monounsaturated, conjugated, highly unsaturated, short-chain types, and their metabolism can impact the development of MetS and associated features. Furthermore, the quality and quantity of dietary fats can influence gut microbiota composition that alters an individual's metabolic health. The gut microbiota modulates components of MetS via different mechanisms. The gut microbiota can swing the host metabolic balance in energy homeostasis, gut motility, appetite, lipid and carbohydrate metabolism, and fat storage in the liver. In addition, an impairment of the gut microbial population by a high-fat diet can lead to systemic inflammation and insulin resistance. The review summarizes the impacts of dietary fats on MetS and their interactions with gut microbiota in modulating the risk factors associated with metabolic syndrome.
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