Group X Secreted Phospholipase A2 Releases ω3 Polyunsaturated Fatty Acids, Suppresses Colitis, and Promotes Sperm Fertility

Abstract

Within the secreted phospholipase A2 (sPLA2) family, group X sPLA2 (sPLA2-X) has the highest capacity to hydrolyze cellular membranes and has long been thought to promote inflammation by releasing arachidonic acid, a precursor of pro-inflammatory eicosanoids. Unexpectedly, we found that transgenic mice globally overexpressing human sPLA2-X (PLA2G10-Tg) displayed striking immunosuppressive and lean phenotypes with lymphopenia and increased M2-like macrophages, accompanied by marked elevation of free ω3 polyunsaturated fatty acids (PUFAs) and their metabolites. Studies using Pla2g10-deficient mice revealed that endogenous sPLA2-X, which is highly expressed in the colon epithelium and spermatozoa, mobilized ω3 PUFAs or their metabolites to protect against dextran sulfate-induced colitis and to promote fertilization, respectively. In colitis, sPLA2-X deficiency increased colorectal expression of Th17 cytokines, and ω3 PUFAs attenuated their production by lamina propria cells partly through the fatty acid receptor GPR120. In comparison, cytosolic phospholipase A2 (cPLA2α) protects from colitis by mobilizing ω6 arachidonic acid metabolites, including prostaglandin E2. Thus, our results underscore a previously unrecognized role of sPLA2-X as an ω3 PUFA mobilizer in vivo, segregated mobilization of ω3 and ω6 PUFA metabolites by sPLA2-X and cPLA2α, respectively, in protection against colitis, and the novel role of a particular sPLA2-X-driven PUFA in fertilization.

Keywords: arachidonic acid (AA) (ARA), colitis, inflammation, lipid metabolism, membrane, Phospholipase A, polyunsaturated fatty acid (PUFA), prostaglandin, sperm

Source : Journal Of Biological Chemistry

ChooseLife : Yet more evidence, of the beneficial properties imbued in individuals, who choose to pay head to Budwig et al. and seek to gain a better balance in their Omega3 to Omega6 ratios. I wouldn’t be without my Flaxoil/Flaxseeds, neither would my… too much!

Floridation Canada Study

https://www.sciencemag.org/news/2019/08/drinking-fluoridated-water-during-pregnancy-may-lower-iq-sons-controversial-study-says

Either way, “It’s a potential bombshell,” says Philippe Grandjean, an environmental health researcher at Harvard University who wasn’t involved in the work.

Why is it a bombshell? given other studies have shown the same results?

Because these scientists fear industry pressure and funding strangulation. Since I found this research I have duck-duck-go searched multiple articles and they are all laced with ‘controversial study’ and ‘too early to start making claims about neurotoxicity, based on one study’, yet this is not the first, there are multiple studies.

Mexico – https://ehp.niehs.nih.gov/doi/10.1289/ehp655

In this study, higher prenatal fluoride exposure, in the general range of exposures reported for other general population samples of pregnant women and nonpregnant adults, was associated with lower scores on tests of cognitive function in the offspring at age 4 and 6–12 y.

India – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5285601/

It is concluded that IQ level was negatively correlated with fluoride level in drinking water. Factors that might affect children’s IQ need to be considered, and it is necessary to devise solutions for preventing the harmful effects of excessive intake of fluoride ion to the body.

Iran – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484826/

Children residing in areas with higher than normal water fluoride levels demonstrated more impaired development of intelligence. Thus, children’s intelligence may be affected by high water fluoride levels.

China – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1852689/

Children’s intelligence and growth can be affected by high concentrations of As or fluoride. 

ChooseLife Notes : Bombshell to who exactly?

Prenatal Fluoride Exposure and Cognitive Outcomes in Children at 4 and 6–12 Years of Age

Abstract

Background:

Some evidence suggests that fluoride may be neurotoxic to children. Few of the epidemiologic studies have been longitudinal, had individual measures of fluoride exposure, addressed the impact of prenatal exposures or involved more than 100 participants.

Objective:

Our aim was to estimate the association of prenatal exposure to fluoride with offspring neurocognitive development.

Methods:

We studied participants from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) project. An ion-selective electrode technique was used to measure fluoride in archived urine samples taken from mothers during pregnancy and from their children when 6–12 y old, adjusted for urinary creatinine and specific gravity, respectively. Child intelligence was measured by the General Cognitive Index (GCI) of the McCarthy Scales of Children’s Abilities at age 4 and full scale intelligence quotient (IQ) from the Wechsler Abbreviated Scale of Intelligence (WASI) at age 6–12.

Results:

We had complete data on 299 mother–child pairs, of whom 287 and 211 had data for the GCI and IQ analyses, respectively. Mean (SD) values for urinary fluoride in all of the mothers (n=299n=299) and children with available urine samples (n=211n=211) were 0.90 (0.35) mg/L0.90 (0.35) mg/L and 0.82 (0.38) mg/L0.82 (0.38) mg/L, respectively. In multivariate models we found that an increase in maternal urine fluoride of 0.5mg/L0.5mg/L (approximately the IQR) predicted 3.15 (95% CI: −5.42−5.42, −0.87−0.87) and 2.50 (95% CI −4.12−4.12, −0.59−0.59) lower offspring GCI and IQ scores, respectively.

Conclusions:

In this study, higher prenatal fluoride exposure, in the general range of exposures reported for other general population samples of pregnant women and nonpregnant adults, was associated with lower scores on tests of cognitive function in the offspring at age 4 and 6–12 y. https://doi.org/10.1289/EHP655