Prostaglandins, leukotrienes, and essential fatty acids最新文献

Background

Fatty acids are involved in bone development but knowledge in children is limited. The aim of this study was to investigate bone mass and mineral density in healthy preschool children in relation to fatty acids.

Material and methods

In 111 healthy 4-yrs-old children (20 % overweight) bone was analysed by dual X-ray absorptiometry and serum phospholipid fatty acid by gas chromatography. Fat intake was calculated from 7 days self-reported dietary records and food frequency questionnaire.

Results

Total bone mass content (BMC) and mineral density (BMD) differed by sex in normal weight, but not in overweight children showing generally higher bone mass density than children with normal weight. Linoleic acid intake was strongly correlated to BMC and femoral BMD in normal weight children. Serum concentration of docosahexaenoic acid correlated positively to BMD in all children (p = 0.01), but linoleic and arachidonic acids, and monounsaturated fatty acids showed diverging associations with bone in normal weight and overweight children.

Conclusion

Serum phospholipid DHA was associated with bone density. Other fatty acids associations to bone sites differed in overweight children, analogue to the pattern in healthy 8-yrs-old.The finding need to be confirmed longitudinally and in a larger group of overweight individuals.

Peroxisome proliferator-activated receptor alpha (PPARα) and antipsychotic medications both influence polyunsaturated fatty acids (PUFA) homeostasis, and thus PPARα polymorphism may be linked to antipsychotic treatment response. Here we investigated whether the functional leucine 162 valine (L162V) polymorphism in PPARα influenced antipsychotic treatment in a group of psychosis patients (N = 186), as well as in a patient subgroup with risperidone, paliperidone, or combination treatment (N = 65). Antipsychotic-naïve first-episode patients and nonadherent chronic individuals were genotyped by polymerase chain reaction analysis. At baseline, and after 8 weeks of treatment with various antipsychotic medications, we assessed the patients’ Positive and Negative Syndrome Scale (PANSS) scores; PANSS factors; and metabolic syndrome-related parameters, including fasting plasma lipid and glucose levels, and body mass index. In the total patient group, PPARα polymorphism did not affect PANSS psychopathology or metabolic parameters. However, in the subgroup of patients with risperidone, paliperidone, or combination treatment, PPARα polymorphism influenced changes in plasma LDL cholesterol. Specifically, compared to PPARα-L162L homozygous patients, PPARα-L162V heterozygous individuals exhibited significantly higher increases of LDL cholesterol levels after antipsychotic treatment. The PPARα polymorphism had a strong effect size, but a relatively weak contribution to LDL cholesterol level variations (∼12.8 %).

The levels of blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are very variable and, in general, low in most of the world population. In this study, the effects of age, sex, COVID-19, and dietary habits on the lipid profile of the erythrocyte membranes were assessed in a sub-cohort of healthy population (N = 203) from a large cohort of individuals from the Basque Country, Spain, (AKRIBEA). Sex did not have an effect on RBC lipid profile. COVID-19 infected participants showed higher levels of DGLA. Oldest participants showed higher oleic acid, EPA and DHA levels. Arachidonic acid in RBC correlated positively with the intake of sunflower oil, butter, eggs, processed and red meat, whereas DHA and EPA correlated positively with oily and lean fish. Basque Country population showed lipid profiles similar to other high fish consuming countries, such as Italy and Japan. Baseline levels of the whole lipidomic profile of the RBC including SFA, MUFA and PUFA should be examined to obtain a better description of the health and nutritional status.

A recent trial showed that high-dose docosahexaenoic acid (high-DHA) supplementation of infants born <29 weeks’ gestation improves intelligence quotient (IQ) at five years’ corrected age. However, this finding has not been detected by other trials of DHA, which either did not measure IQ or included more mature infants. We analyzed the subgroup of 204 infants born <29 weeks’ from our earlier randomized trial of high-DHA (∼1 % total fatty acids) or standard-DHA (∼ 0.3 % total fatty acids). Participants were assessed for cognition at 18 months, and IQ and behavior at seven years’ corrected age. No group differences were detected for mean cognitive, IQ or behavior scores. At 18 months, 18.8 % of children in the high-DHA group had a cognitive score <85, compared with 31.1 % of children in the standard-DHA group, but at seven years there was no difference. Although an underpowered post-hoc subgroup analysis, this study provides limited support to recommendations that infants born <29 weeks’ gestation require supplemental DHA.

In bone, prostaglandin E₂ (PGE₂) is highly osteogenic and formed by osteoblasts, a key modulatory event in the regulation of bone cell activity. MC3T3-E1 cells are widely used as an in vitro model of osteoblast function. It is still not clear which pathways contribute to the release of AA in these cells. In this study we have focussed on the contribution of phospholipase D (PLD) enzymes to osteoblastic PGE₂ formation after stimulation with endothelin-1 (ET-1). Using specific inhibitors of PLD1 and PLD2 we could show that PGE₂ formation was strictly dependent on PLD1 but not PLD2 activity and cytosolic phospholipase A₂ (cPLA₂) was activated by triggering through PLD1. We have identified diacyl glycerol (DAG) as a possible effector molecule which may serve as a triggering signal for PKC activation and subsequent cPLA₂ phosphorylation.

Parametric tests such as t-tests require a normal distribution of data. However, the determination of normal distribution may not be conclusive while dealing with a small sample size. Non-parametric tests such as Wilcoxon tests may be used in this situation, as these tests do not require normal distribution.

Early dietary long-chain n-3PUFA (n-3LCPUFA) may affect brain development. We investigated if fish oil supplementation of lactating mothers affected socioemotional wellbeing in adolescents in a potentially gender-specific manner. At age 13, we invited 92 children of mothers who completed a randomized trial with 1.5 g/d n-3 LCPUFA or olive oil during the first 4 months of lactation and 48 children of mothers with a high habitual fish intake. Children and parents answered validated questionnaires regarding socioemotional wellbeing and physical activity was monitored by ActiGraph for 7 days. Participation rate was 71%. Univariate correlations between children's and parents’ ratings on the individual scales were moderate-strong, but correlations across questionnaires indicated that parents might base their ratings on proxy markers. We found no group differences in self-rated socioemotional outcomes or physical activity. Although the study was small, it was the first follow-up on effects of perinatal n-3LCPUFA supply on socioemotional wellbeing in adolescence.

Background

The role of the lipoxygenase (LOX) and cyclooxygenase (COX) enzymes in maintaining cellular homeostasis and regulating immune responses promoted us in this study to analyze the pattern of changes in 15-lipoxygenase and cyclooxygenase isoforms and their related cytokines in SARS-CoV-2 infection.

Methods

15-LOX-1, 15-LOX-2, COX-1 and COX-2 gene expression levels were determined using qRT-PCR in nasopharynx specimens from patients with severe [N = 40] and non-severe [N = 40] confirmed SARS-CoV-2 infections and healthy controls. Circulating levels of lL-6, lL-10, PGE2, and IFN-γ were measured in patients and healthy controls using ELISA assay. The associations between the measured variables and the patient's clinic-pathological characteristics were assessed for all groups.

Results

The expression level of 15-LOX-1 was elevated significantly in male patients with severe infection; although female patients showed a different expression profile. 15-LOX-2 expression level was considerably increased in male patients with severe infection; while changes in its expression remained inconclusive in female patients. The relationship between 15-LOX expression and the male gender was prominent. Both COX isoforms expression showed elevation in male and female patients that were correlated with disease severity. The simultaneous increase in lL-6, PGE2 and IFN-γ levels also decrease in lL-10 in patients with severe infection indicating the possible regulatory network related to the COX and 15-LOX enzymes in the output of the SARS-CoV-2 infection.

Conclusion

The results of this study determined the pattern of possible changes in key enzymes of prostaglandin and eicosanoids synthesis pathway and their mediators, which can be helpful in mapping the SARS-CoV-2 pathogenicity and pharmaceutical approaches.