The imperative of arachidonic acid in early human development

Crawford, Mike; Sinclair, Andrew J.; Hall, Barbara; Ogundipe, Enitan; Wang, Yudong; Bitsanis, Dimitrios; Djahanbakhch, O.; Harbige, Laurence S.; Golfetto, Iván; Moodley, Therishnee; Hassam, A. G.; Sassine, AnnieBelle J.; Johnson, Mark R.

doi:10.1016/j.plipres.2023.101222

Cited by 29 publications

(11 citation statements)

References 140 publications

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“…This is equivalent to a maximum of 2.4 mg per 5 μl supplement and may impact on the final endogenous concentration of AA. Nonetheless, that contribution is likely limited, as supplemented linoleic acid contributes to tissue AA one order of magnitude less than supplemented AA (reviewed in [ 6 ]). Likewise, increased levels of dietary linoleic acid are not associated with increases in tissue AA content [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

Effects of paternal arachidonic acid supplementation on offspring behavior and hypothalamus inflammation markers in the mouse

Vázquez-Sánchez,

Rodríguez-Ríos,

Colín-Castelán

et al. 2024

PLoS ONE

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Arachidonic acid (AA) is involved in inflammation and plays a role in growth and brain development in infants. We previously showed that exposure of mouse sires to AA for three consecutive generations induces a cumulative change in fatty acid (FA) involved in inflammation and an increase in body and liver weight in the offspring. Here, we tested the hypothesis that paternal AA exposure changes the progeny’s behavioral response to a proinflammatory insult, and asked whether tissue-specific FA are associated with that response. Male BALB/c mice were supplemented daily with three doses of AA for 10 days and crossed to non-supplemented females (n = 3/dose). Two-month-old unsupplemented male and female offspring (n = 6/paternal AA dose) were exposed to Gram-negative bacteria-derived lipopolysaccharides (LPS) or saline control two hours prior to open field test (OFT) behavioral analysis and subsequent sacrifice. We probed for significant effects of paternal AA exposure on: OFT behaviors; individual FA content of blood, hypothalamus and hypothalamus-free brain; hypothalamic expression profile of genes related to inflammation (Tnfa, Il1b, Cox1, Cox2) and FA synthesis (Scd1, Elovl6). All parameters were affected by paternal AA supplementation in a sex-specific manner. Paternal AA primed the progeny for behavior associated with increased anxiety, with a marked sex dimorphism: high AA doses acted as surrogate of LPS in males, realigning a number of OFT behaviors that in females were differential between saline and LPS groups. Progeny hypothalamic Scd1, a FA metabolism enzyme with documented pro-inflammatory activity, showed a similar pattern of differential expression between saline and LPS groups at high paternal AA dose in females, that was blunted in males. Progeny FA generally were not affected by LPS, but displayed non-linear associations with paternal AA doses. In conclusion, we document that paternal exposure to AA exerts long-term behavioral and biochemical effects in the progeny in a sex-specific manner.

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Section: Methodsmentioning

confidence: 99%

Effects of paternal arachidonic acid supplementation on offspring behavior and hypothalamus inflammation markers in the mouse

Vázquez-Sánchez,

Rodríguez-Ríos,

Colín-Castelán

et al. 2024

PLoS ONE

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“…The expression of many lipid-related substances changed in this study. Fatty acid metabolism have been found to affect on the proin ammatory properties and the aggregation of platelets [30][31] . A growing body of evidence suggests that essential fatty acids and their active metabolic byproducts play a crucial role in maintaining the structural and functional integrity of both the central nervous system.…”

Section: Discussionmentioning

confidence: 99%

Mild-iodine-deficiency based on 24-hour urinary iodine excretion leads to significant metabolic changes in pregnant women at early stages of pregnancy

Fan,

Bu,

Liu

et al. 2024

Preprint

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The effects of mild iodine deficiency during the first and second trimesters on both pregnant women themselves and their offspring exhibited in consistent patterns. In this study, we aimed to address this issue by employing small molecule metabolomics. A total of 98 pregnant women in either the first or second trimester were recruited, with comprehensive data including basic information, 24-hour urine samples and blood samples collected, and subsequent evaluation of birth outcomes for their offspring. The 24-hour urinary iodine excretion (UIE) was detected and used as the dividing criterion to determine the iodine nutrition status of pregnant women. Serum metabolomics assay was performed by Ultra High Performance Liquid Chromatography Orbitrap Exploris Mass Spectrometry (UHPLC-OE-MS) platform. Differential metabolites as the potential iodine deficiency biomarkers were selected by multivariate statistical analysis methods. Association analysis was used to further analyze the relationship between the potential biomarkers and neonatal birth outcomes. As a result, there was no significant difference in maternal thyroid function indicators and neonatal outcomes between mild iodine deficiency and iodine adequate pregnant women. However, the metabolic profile of pregnant women with mild iodine deficiency was significantly disturbed compare to these with iodine adequate. A total of 28 different metabolites were screened, which could be used as the potential biomarkers of iodine deficiency. After adjusted age and pregnancy trimester, the expression of these biomarkers were also changed significantly. Furthermore, these markers were also related to fatty acid biosynthesis, tyrosine metabolism, tryptophan metabolism, arachidonic acid metabolism, and pentose and glucuronate interconversions. In addition, among these markers, 2-(4-Methyl-5-thiazolyl)ethyl octanoate was found to be associated with neonatal TSH, ACar(12:0), (9S,10E,12Z,15Z)-9-Hydroxy-10,12,15-octadecatrienoic acid showed a correlation with body length; whereas (9S,10E,12Z,15Z)-9-Hydroxy-10,12,15-octadecatrienoic acid was linked to body weight. In conclusion, mild iodine deficiency during the first and second trimesters dose not result in overt adverse effects on pregnant women and their offspring. However, at the metabolic level, mild iodine deficiency may disrupt the metabolic profile of pregnant women and impact the development of their offspring.

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“…190 These factors are closely related to ovulation, menstruation, pregnancy, and childbirth and the occurrence of the physiological inflammatory response. 191,192 AA metabolism is essential for oocyte maturation. The maturation of oocyte meiosis is one of the important physiological requirements for ovulation and fertility.…”

Section: Aa Metabolism In Germ Cell Developmentmentioning

confidence: 99%

“…AA and LA are very important during pregnancy 190 . These factors are closely related to ovulation, menstruation, pregnancy, and childbirth and the occurrence of the physiological inflammatory response 191,192 …”

Section: Aa Metabolism In Human Health and Diseasesmentioning

confidence: 99%

Arachidonic acid metabolism in health and disease

Zhang,

Liu,

Sun

et al. 2023

MedComm

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Arachidonic acid (AA), an n‐6 essential fatty acid, is a major component of mammalian cells and can be released by phospholipase A2. Accumulating evidence indicates that AA plays essential biochemical roles, as it is the direct precursor of bioactive lipid metabolites of eicosanoids such as prostaglandins, leukotrienes, and epoxyeicosatrienoic acid obtained from three distinct enzymatic metabolic pathways: the cyclooxygenase pathway, lipoxygenase pathway, and cytochrome P450 pathway. AA metabolism is involved not only in cell differentiation, tissue development, and organ function but also in the progression of diseases, such as hepatic fibrosis, neurodegeneration, obesity, diabetes, and cancers. These eicosanoids are generally considered proinflammatory molecules, as they can trigger oxidative stress and stimulate the immune response. Therefore, interventions in AA metabolic pathways are effective ways to manage inflammatory‐related diseases in the clinic. Currently, inhibitors targeting enzymes related to AA metabolic pathways are an important area of drug discovery. Moreover, many advances have also been made in clinical studies of AA metabolic inhibitors in combination with chemotherapy and immunotherapy. Herein, we review the discovery of AA and focus on AA metabolism in relation to health and diseases. Furthermore, inhibitors targeting AA metabolism are summarized, and potential clinical applications are discussed.

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The imperative of arachidonic acid in early human development

Cited by 29 publications

References 140 publications

Effects of paternal arachidonic acid supplementation on offspring behavior and hypothalamus inflammation markers in the mouse

Effects of paternal arachidonic acid supplementation on offspring behavior and hypothalamus inflammation markers in the mouse

Mild-iodine-deficiency based on 24-hour urinary iodine excretion leads to significant metabolic changes in pregnant women at early stages of pregnancy

Arachidonic acid metabolism in health and disease

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