Serum Arachidonic Acid Research Articles

Association between Preoperative Long-Chain Polyunsaturated Fatty Acids and Oxidative Stress Immediately after Total Knee Arthroplasty: A Pilot Study.

Quadriceps muscle atrophy following total knee arthroplasty (TKA) can be caused by tourniquet-induced ischemia–reperfusion (IR) injury, which is often accompanied by oxidative stress and inflammatory responses. n-3 long-chain polyunsaturated fatty acids (LCPUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exert antioxidant and anti-inflammatory effects against IR injury, whereas n-6 LCPUFAs, particularly arachidonic acid (AA), exhibit pro-inflammatory effects and promote IR injury. This study aimed to examine whether preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio are associated with oxidative stress immediately after TKA. Fourteen eligible patients with knee osteoarthritis scheduled for unilateral TKA participated in this study. The levels of serum EPA, DHA, and AA were measured immediately before surgery. Derivatives of reactive oxygen metabolites (d-ROMs) were used as biomarkers for oxidative stress. The preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio were found to be significantly negatively correlated with the serum d-ROM levels at 96 h after surgery, and the rate of increase in serum d-ROM levels between baseline and 96 h postoperatively. This study suggested the preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio can be negatively associated with oxidative stress immediately after TKA.

Abstract P450: Serum Arachidonic Acid Levels in Relation With Outcome of Acute Intracerebral Hemorrhage

Introduction: The correlation between serum polyunsaturated fatty acids (PUFAs) such as Eicosapentaenoic Acid (EPA), Docosahexaenoic Acid (DHA), Arachidonic Acid (AA) and Dihomogammalinolenic Acid (DHLA) levels and clinical outcomes of cardiovascular disease are previously reported. The aim was to investigate serum PUFAs including AA levels to clinical outcome in intracerebral hemorrhage (ICH) patients. Method: From Nov 2012 to Nov 2019, ICH patients within 24 hours from the onset were enrolled. All patients underwent radiological investigations and laboratory examinations including measurement of serum PUFAs levels on admission. We divided patients into two groups, favorable outcome group (mRS at 3 months 0-3) and poor outcome group (mRS at 3 months 4-6). We compared baseline variables including serum PUFAs levels between two groups. Result: We enrolled 142patients (87 male, median age 60 years old, median NIHSS score 8). Of them, 113 patients (80%) were favorable outcome group and 29 patients (20%) were poor outcome group. Higher NIHSS score and larger size of hematoma on admission were found in poor outcome group (median NIHSS score 6 of favorable outcome vs. 14 of poor outcome, p<0.001, and median hematoma size, 7.5ml vs. 13.5ml, p=0.048). In serum PUFAs levels, only serum AA levels was significantly lower in poor outcome group (median interval 213μg/ml vs. 179μg/ml, p=0.002) though there were no difference of DHLA, EPA and DHA levels between two groups. In multivariate logistic regression analysis, lower serum AA levels was independently associated with poor outcome (OR 0.987, 95%CI 0.978-0.996, p=0.007, Figure). Conclusion: Serum AA levels may play an important role in predicting the outcome in ICH.

Serum Eicosapentaenoic and Arachidonic Acids Concentration and Cognitive Function in Patients With Coronary Artery Disease.

Introduction:Recent studies have shown that Polyunsaturated Fatty Acids (PUFAs), including Eicosapentaenoic Acid (EPA), and Arachidonic Acid (AA), are associated with cognitive functions in patients with Coronary Artery Disease (CAD). Nevertheless, controversial results have been reported, too. The current study aimed to clarify the association of serum EPA and AA levels with cognitive decline in an Iranian sample with CAD.Methods:We evaluated cognitive function with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), in relation to serum levels of EPA and AA, in 179 CAD patients. The associations between the MMSE and MoCA scores and the other demographic parameters were evaluated.Results:Patients with CAD generally had mild cognitive impairment. But we could not find any significant correlation between PUFAs and cognitive function. However, BMI was associated with EPA/MoCA; age was associated with MMSE/MoCA and BMI. Finally, the correlation between sex and MMSE/MoCA was significant.Conclusion:Subjects generally had mild cognitive impairment, but we could not find any significant correlation between serum EPA and AA levels with cognitive function.

PCTR1 ameliorates lipopolysaccharide-induced acute inflammation and multiple organ damage via regulation of linoleic acid metabolism by promoting FADS1/FASDS2/ELOV2 expression and reducing PLA2 expression

Gram-negative bacterial infection causes an excessive inflammatory response and acute organ damage or dysfunction due to its outer membrane component, lipopolysaccharide (LPS). Protectin conjugates in tissue regeneration 1 (PCTR1), an endogenous lipid mediator, exerts fundamental anti-inflammation and pro-resolution during infection. In the present study, we examined the properties of PCTR1 on the systemic inflammatory response, organic morphological damage and dysfunction, and serum metabolic biomarkers in an LPS-induced acute inflammatory mouse model. The results show that PCTR1 reduced serum inflammatory factors and ameliorated morphological damage and dysfunction of the lung, liver, kidney, and ultimately improved the survival rate of LPS-induced acute inflammation in mice. In addition, metabolomics analysis and high performance liquid chromatography-mass spectrometry revealed that LPS-stimulated serum linoleic acid (LA), arachidonic acid (AA), and prostaglandin E2 (PGE2) levels were significantly altered by PCTR1. Moreover, PCTR1 upregulated LPS-inhibited fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2), and elongase of very long chain fatty acids 2 (ELOVL2) expression, and downregulated LPS-stimulated phospholipase A2 (PLA2) expression to increase the intrahepatic content of AA. However, these effects of PCTR1 were partially abrogated by a lipoxin A4 receptor (ALX) antagonist (BOC-2). In summary, via the activation of ALX, PCTR1 promotes the conversion of LA to AA through upregulation of FADS1, FADS2, and ELOVL2 expression, and inhibits the conversion of bound AA into free AA through downregulation of PLA2 expression to decrease the serum AA and PGE2 levels.

Sterol Carrier Protein-2/Sterol Carrier Protein-x/Fatty Acid Binding Protein-1 Ablation Impacts Response of Brain Endocannabinoid to High-Fat Diet.

Brain endocannabinoids (EC) such as arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) primarily originate from serum arachidonic acid (ARA), whose level is regulated in part by a cytosolic ARA-binding protein, that is, liver fatty acid binding protein-1 (FABP1), not expressed in the brain. Ablation of the Fabp1 gene (LKO) increases brain AEA and 2-AG by decreasing hepatic uptake of ARA to increase serum ARA, thereby increasing ARA availability for uptake by the brain. The brain also expresses sterol carrier protein-2 (SCP-2), which is also a cytosolic ARA-binding protein. To further resolve the role of SCP-2 independent of FABP1, mice ablated in the Scp-2/Scp-x gene (DKO) were crossed with mice ablated in the Fabp1 gene (LKO) mice to generate triple knock out (TKO) mice. TKO impaired the ability of LKO to increase brain AEA and 2-AG. While a high-fat diet (HFD) alone increased brain AEA, TKO impaired this effect. Overall, these TKO-induced blocks were not attributable to altered expression of brain proteins in ARA uptake, AEA/2-AG synthesis, or AEA/2-AG degrading enzymes. Instead, TKO reduced serum levels of free ARA and/or total ARA and thereby decreased ARA availability for uptake to the brain and downstream synthesis of AEA and 2-AG therein. In summary, Scp-2/Scp-x gene ablation in Fabp1 null (LKO) mice antagonized the impact of LKO and HFD on brain ARA and, subsequently, EC levels. Thus, both FABP1 and SCP-2 participate in regulating the EC system in the brain.

Eicosapentaenoic acid/arachidonic acid ratio and weight loss during hospitalization for glycemic control among overweight Japanese patients with type 2 diabetes: a retrospective observational study

BackgroundThe study aimed to examine the relationship between levels of serum eicosapentaenoic acid (EPA), arachidonic acid (AA), as well as EPA/AA ratio and weight loss during hospitalization in participants considered to be overweight, with type 2 diabetes.MethodsThe study participants included 142 patients who were hospitalized for treatment of type 2 diabetes. We divided the participants into two groups depending on the achievenemt in reduction of bodyweight 3% or more during hospitalization and examined the relationship between serum levels of EPA and AA, as well as ratio of EPA/AA on admission and effectiveness of weight loss under strict dietary therapy during hospitalization, using Cox proportional hazard models.ResultsAfter adjustment was made for several confounders, the hazard ratio of effective weight loss for logarithmical serum EPA was 1.59 (95% CI 1.02–2.49, P = 0.04) and for logarithmical EPA/AA ratio 1.64 (1.03–2.61, P = 0.04), whereas the hazard ratio for effective weight loss for logarithmical serum AA was 1.11 (0.45–2.78, P = 0.82). In addition, after dividing EPA/AA ratio and serum EPA into quartiles based on participant number, the hazard ratio for the highest quartile of EPA/AA ratio was 2.33 (1.14–4.77, P = 0.02), and for the highest quartile of serum EPA 1.60 (0.80–3.19, P = 0.18) compared with the lowest quartile.ConclusionThese results suggest the possibility that EPA is involved in bodyweight change under a caloric-restriction regimen. In addition, EPA/AA ratio was found to be a better predictor of medical intervention for weight loss among overweight patients with type 2 diabetes, compared with serum EPA level.

Metabolomic alterations associated with Beh\xe7et\u2019s disease

BackgroundThe diagnosis of Behçet’s disease (BD) remains challenging due to the lack of diagnostic biomarkers. This study aims to identify potential serum metabolites associated with BD and its disease activity.MethodsMedical records and serum samples of 24 pretreated BD patients, 12 post-treated BD patients, and age-matched healthy controls (HC) were collected for metabolomics and lipidomics profiling using UPLC-QTOF-MS and UPLC-QTOF-MSE approaches. Additionally, serum samples from an independent cohort of BD patients, disease controls including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Takayasu’s arteritis (TA), Crohn’s disease (CD) patients, and HC were collected for further validation of two potential biomarkers using UPLC-QTOFMS analysis.ResultsUnsupervised principal component analysis (PCA) showed a clear separation of metabolomics profiles of BD patients from HC. Statistical analysis of the data revealed differential metabolites between BD patients and HC. The serum levels of some phosphatidylcholines (PCs) were found to be significantly lower in BD patients, while the levels of several polyunsaturated fatty acids (PUFAs) were increased markedly in the BD group compared with HC. Furthermore, the serum level of two omega-6 PUFAs, linoleic acid (LA) and arachidonic acid (AA), were dramatically decreased in patients with remission. A validation cohort confirmed that the serum LA and AA levels in BD patients were significantly higher than those in HC and patients with RA, SLE, TA, and CD. In addition, receiver operating characteristic (ROC) analysis indicated good sensitivity and specificity.ConclusionsThe serum metabolomics profiles in BD patients are altered. Serum LA and AA are promising diagnostic biomarkers for BD.

Association between the ratio of serum arachidonic acid to eicosapentaenoic acid and the presence of depressive symptoms in a general Japanese population: the Hisayama Study

BackgroundEpidemiological evidence suggests that fish consumption and intake of n-3 polyunsaturated fatty acids (PUFA)—namely, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—confer protection against depression. However, few studies have addressed the influence of the balance between n-3 PUFA and n-6 PUFA in the human body on depression. MethodsA total of 2,529 community-dwelling Japanese residents aged ≥ 40 years were assessed for depressive symptoms (defined as a score of 16 points or more on the Center for Epidemiologic Studies Depression Scale [CES-D]) in 2007. The serum arachidonic acid (AA) /EPA ratio and AA/DHA ratio were measured in frozen samples collected in 2002 and categorized into quartiles. The odds ratios (ORs) for the presence of depressive symptoms were calculated using a logistic regression model. ResultsThe prevalence of depressive symptoms was 4.3%. There was no significant association between either the serum AA/EPA ratio or AA/DHA ratio and the presence of depressive symptoms. However, subjects with the highest serum AA/EPA ratios (range: 3.28–13.3) had a 4.10 times (95%CI: 1.13–19.80) greater OR for the presence of depressive symptoms than those with the lowest ratios (0.30–1.65) after adjusting for confounding factors in the subgroup with high-sensitivity C-reactive protein (hs-CRP) ≥ 1.0 mg/L, while no clear association was observed in the subgroup with hs-CRP < 1.0 mg/L. LimitationsReverse causality is possible due to the cross-sectional study design. ConclusionsOur findings suggest that a higher serum AA/EPA ratio is associated with a greater likelihood of depressive symptoms in subjects with systemic inflammation in the general Japanese population.

Influence of Human Milk and Parenteral Lipid Emulsions on Serum Fatty Acid Profiles in Extremely Preterm Infants.

BackgroundInfants born prematurely are at risk of a deficiency in ω‐6 and ω‐3 long‐chain polyunsaturated fatty acids (LC‐PUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA). We investigated how fatty acids from breast milk and parenteral lipid emulsions shape serum LC‐PUFA profiles in extremely preterm infants during early perinatal life.MethodsNinety infants born < 28 weeks gestational age were randomized to receive parenteral lipids with or without the ω‐3 LC‐PUFAs eicosapentaenoic acid (EPA) and DHA (SMOFlipid: Fresenius Kabi, Uppsala, Sweden, or Clinoleic: Baxter Medical AB, Kista, Sweden, respectively). The fatty acid composition of infant serum phospholipids was determined from birth to postmenstrual age 40 weeks, and in mother's milk total lipids on postnatal day 7. Enteral and parenteral intake of LC‐PUFAs was correlated with levels in infant serum.ResultsInfants administered parenteral ω‐3 LC‐PUFAs received 4.4 and 19.3 times more DHA and EPA, respectively, over the first 2 weeks of life. Parenteral EPA but not DHA correlated with levels in infant serum. We found linear relationships between dietary EPA and DHA and infant serum levels in the Clinoleic (Baxter Medical AB) group. The volume of administered SMOFlipid (Fresenius Kabi) was inversely correlated with serum AA, whereas Clinoleic (Baxter Medical AB) inversely correlated with serum EPA and DHA.ConclusionsThere appears to be no or low correlation between the amount of DHA administered parenterally and levels measured in serum. Whether this observation reflects serum phospholipid fraction only or truly represents the amount of accreted DHA needs to be investigated. None of the parenteral lipid emulsions satisfactorily maintained high levels of both ω‐6 and ω‐3 LC‐PUFAs in infant serum.

Serum n–6 polyunsaturated fatty acids and risk of death: the Kuopio Ischaemic Heart Disease Risk Factor Study

The cardioprotective properties of linoleic acid (LA), a major n-6 (ω-6) polyunsaturated fatty acid (PUFA), have been recognized, but less is known about its associations with other causes of death. Relatively little is also known about how the minor n-6 PUFAs-γ-linolenic acid (GLA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA)-relate to mortality risk. We investigated the associations of serum n-6 PUFAs, an objective biomarker of exposure, with risk of death in middle-aged and older men and whether disease history modifies the associations. We included 2480 men from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 y at baseline in 1984-1989. The stratified analyses by baseline disease status included 1019 men with a history of cardiovascular disease (CVD), cancer, or diabetes and 1461 men without a history of disease. During the mean follow-up of 22.4 y, 1143 deaths due to disease occurred. Of these, 575 were CVD deaths, 317 were cancer deaths, and 251 were other-cause deaths. A higher serum LA concentration was associated with a lower risk of death from any cause (multivariable-adjusted HR for the highest compared with the lowest quintile: 0.57; 95% CI: 0.46, 0.71; P-trend<0.001) and with deaths due to CVD (extreme-quintile HR: 0.54; 95% CI: 0.40, 0.74; P-trend<0.001) and non-CVD or noncancer causes (HR: 0.48; 95% CI: 0.30, 0.76; P-trend=0.001). Serum AA had similar, although weaker, inverse associations. Serum GLA and DGLA were not associated with risk of death, and none of the fatty acids were associated with cancer mortality. The results were generally similar among those with or without a history of major chronic disease (P-interaction>0.13). Our findings showed an inverse association of a higher biomarker of LA intake with total and CVD mortality and little concern for risk, thus supporting the current dietary recommendations to increase LA intake for CVD prevention. The finding of an inverse association of serum AA with the risk of death needs replication in other populations.

The Clinical Significance of Low Serum Arachidonic Acid in Sepsis Patients with Hypoalbuminemia.

Objectives Fatty acids (FAs) have various roles in pro-inflammatory and anti-inflammatory functions. Hypoalbuminemia is often observed in sepsis patients. An imbalance among these compounds formed from FAs caused by hypoalbuminemia may be related to increased mortality in sepsis patients. The purpose of this study was to investigate the correlations between serum albumin and FAs in sepsis and the outcome. Methods This study was an observational investigation. The clinical and laboratory data of sepsis patients were recorded and the Sequential Organ Failure Assessment (SOFA) score was calculated at admission. The serum arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and dihomo-gamma-linolenic acid (DHLA) levels were also measured as FAs. The body mass index (BMI) was used to determine the general nutrition status. Results Two hundred sepsis patients were enrolled during the study period. No significant correlations were observed between the BMI and the SOFA score or the serum albumin level at admission. The FA levels of the non-survivors were significantly lower, but there were no significant differences in the EPA/AA levels of the survivors and non-survivors. A low serum albumin level was closely related to low AA (p<0.0001), EPA (p<0.0001), DHA (p=0.0003), and DHLA levels (p<0.0001). A multiple logistic-regression analysis revealed that a high SOFA score [adjusted odds ratio, 1.19; 95% confidence interval (CI), 1.02-1.39, p=0.026] and low AA (adjusted odds ratio, 0.98; 95% CI, 0.978-0.994, p=0.041) were associated with a poor outcome. Conclusion A lower AA level was an important determinant of the outcome of patients with sepsis. These findings are consistent with the findings of previous studies, which reported that hypoalbuminemia might alter the AA metabolism in sepsis patients.

Is arachidonic acid an endoschistosomicide?

Schistosoma mansoni and Schistosoma haematobium are intravascular, parasitic flatworms that infect >250 million people in 70 developing countries, yet not all people of the same community and household are afflicted. Regarding laboratory rodents, mice but not rats are susceptible to infection with S. mansoni and hamsters but not mice are entirely permissive to infection with S. haematobium. A recent Brazilian publication has demonstrated that resistance of the water-rat, Nectomys squamipes to S. mansoni infection might be ascribed to stores of arachidonic acid (ARA)-rich lipids in liver. Several reports have previously shown that ARA is a safe and effective schistosomicide in vitro, and in vivo in mice, hamsters and in children. Schistosoma haematobium appeared more sensitive than S. mansoni to ARA in in vitro and in vivo experiments. Accordingly, it was proposed that ARA increased levels might be predominantly responsible for natural attrition of S. mansoni and S. haematobium in resistant experimental rodents. Therefore, the levels of ARA in serum, lung, and liver of rats (resistant) and mice (susceptible) at 1, 2, 3, 4 and 6 weeks after infection with S. mansoni cercariae and between mice (semi-permissive) and hamster (susceptible) at 1, 2, 3, 4, and 12 weeks after infection with S. haematobium cercariae were compared and contrasted. Neutral triglycerides and ARA levels were assessed in serum using commercially available assays and in liver and lung sections by transmission electron microscopy, Oil Red O staining, and specific anti-ARA antibody-based immunohistochemistry assays. Significant (P < .05), consistent, and reproducible correlation was recorded between ARA content in serum, lung, and liver and rodent resistance to schistosome infection, thereby implicating ARA as an endoschistosomicide.

Age Stratification and Impact of Eicosapentaenoic Acid and Docosahexaenoic Acid to Arachidonic Acid Ratios in Ischemic Stroke Patients.

Aim: We focused on the ratios of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to arachidonic acid (AA) and explored the significance of these ratios relative to clinical characteristics by age in ischemic stroke patients.Methods: We enrolled patients with acute ischemic stroke who underwent radiological investigations and laboratory examinations, including measurement of serum EPA, DHA, and AA levels, and controls. Patients were classified according to age (< 65, 65–74, and ≥ 75 years) and the tertile of EPA/AA and DHA/AA ratios, and clinical aspects were compared with these factors.Results: We analyzed 373 patients (age 70.2 ± 13.4 years; 245 males) and 105 controls. Among stroke patients, patients aged < 65 years had the lowest EPA/AA (0.35 ± 0.23, p = 0.006) and DHA/AA (0.73 ± 0.27, p < 0.001) ratios. Compared with controls, patients aged < 65 years showed lower EPA/AA (vs. 0.49 ± 0.25, p < 0.001) and DHA/AA (vs. 0.82 ± 0.26, p = 0.009) ratios. From logistic regression analysis, the EPA/AA (odds ratio 0.18, 95% confidence interval 0.04–0.81, p = 0.026) and DHA/AA (odds ratio 0.09, 95% confidence interval 0.02–0.33, p < 0.001) ratios were inversely related to patients aged < 65 years. According to age-stratified analyses, we found an association of aortic arch calcification with a lower EPA/AA ratio for patients aged ≥ 75 years and an association of multiple infarctions and cerebral white matter lesions with a lower EPA/AA ratio for patients aged 65–74 years (p < 0.05).Conclusions: The ratios of EPA/AA and DHA/AA could be specific markers for younger stroke patients. The EPA/AA ratio may be related to aortic arch calcification for elderly stroke patients and to multiple infarctions and cerebral white matter disease for middle-aged stroke patients.

The ratio of serum eicosapentaenoic acid to arachidonic acid and riskof cancer death in a Japanese community: The Hisayama Study.

BackgroundWhether the intake of eicosapentaenoic acid (EPA) or arachidonic acid (AA) affects the risk of cancer remains unclear, and the association between the serum EPA:AA ratio and cancer risk has not been fully evaluated in general populations.MethodsA total of 3098 community-dwelling subjects aged ≥40 years were followed up for 9.6 years (2002–2012). The levels of the serum EPA:AA ratio were categorized into quartiles (<0.29, 0.29–0.41, 0.42–0.60, and >0.60). The risk estimates were computed using a Cox proportional hazards model. The same analyses were conducted for the serum docosahexaenoic acid to arachidonic acid (DHA:AA) ratio and individual fatty acid concentrations.ResultsDuring the follow-up period, 121 subjects died of cancer. Age- and sex-adjusted cancer mortality increased with lower serum EPA:AA ratio levels (P trend<0.05). In the multivariable-adjusted analysis, the subjects in the first quartile of the serum EPA:AA ratio had a 1.93-fold (95% confidence interval, 1.15–3.22) greater risk of cancer death than those in the fourth quartile. Lower serum EPA concentrations were marginally associated with higher cancer mortality (P trend<0.11), but the serum DHA or AA concentrations and the serum DHA:AA ratio were not (all P trend>0.37). With regard to site-specific cancers, lower serum EPA:AA ratio was associated with a higher risk of death from liver cancer. However, no such associations were detected for deaths from other cancers.ConclusionsThese findings suggest that decreased level of the serum EPA:AA ratio is a significant risk factor for cancer death in the general Japanese population.

The Effect of Prepartum Adiposity and Lipolysis on Gestational and Postnatal Oxylipids Biosynthesis

Gestational diabetes is associated with increased lipolysis and adipose tissue (AT) inflammation, which impair insulin signaling during the second half of pregnancy and in early lactation. Prevalence of gestational diabetes is high in overweight and obese women; similarly, dairy cows with high adiposity exhibit a surge in AT lipolysis and inflammatory responses during the last trimester of gestation that lead to AT insulin resistance. Oxidized FA (oxylipids) can modulate inflammatory responses during lipolysis. Linoleic acid (LNA) and arachidonic acid (AA) derived oxylipids, including hydroxy‐octadecadienoic acids (HODE), oxo‐octadecadienoic acids (oxoODE), and hydroxy‐eicosatetraenoic acids (HETE), were recently identified as potential biomarkers for early detection of insulin resistance. However, the effects of adiposity and lipolysis rate during late gestation and early lactation on oxylipid biosynthesis including FA substrate availability is currently unknown. We hypothesized that periparturient profiles of serum and AT concentrations of PUFA and oxylipids are dependent on body adiposity and lipolytic rate. Blood and subcutaneous AT samples were collected from multiparous Holstein cows with high (HA; n=5) or low (LA; n=4) adiposity scores at −27±7 (FO) and −10±5 (CU) d prepartum and at 8±3 d postpartum (PP). Targeted lipidomic analysis was performed on plasma and AT using HPLC‐MS/MS. We report that circulating free FA (FFA) concentrations increased as parturition approached, and peaked at PP. Across time, HA increased the concentration of circulating FFA compared to LA, reflecting a significant effect of adiposity on lipolytic rate during the periparturient period. Serum concentrations of AA and eicosapentanoic acid (EPA) were decreased at CU, compared to the other timepoints for all cows. Across time, serum AA and docosahexanoic acid (DHA) concentrations were decreased in HA compared to LA. AT content of AA and DHA, as well as LNA content in AT and serum, were unchanged throughout the study and were not influenced by adiposity. There were effects of both adiposity and timepoint on oxylipid concentrations. In AT, 13‐HODE, 5‐HETE, and 11‐HETE were increased at PP compared to FO and CU. Compared to LA, HA had decreased AT concentrations of 9‐HODE,13‐HODE, 5‐HETE, and 15‐HETE. Serum concentration of 9‐oxoODE was increased at PP and was positively correlated with serum FFA concentration (r=0.52. P=0.01), but was unaffected by adiposity. These data demonstrate that prepartum adiposity may limit the availability of serum PUFA, such as DHA, which serve as substrates for anti‐inflammatory oxylipids. Furthermore, lipolysis during late gestation and the onset of lactation may enhance AT biosynthesis and systemic release of HODE and HETE into circulation.Support or Funding InformationUSDA‐NIFA grants 2014‐68004‐21972 and 2015‐67015‐23207Michigan Alliance for Animal Agriculture Effect of adiposity and sampling time point across late gestation and early lactation on fatty add composition and oxylipid profile of subcutaneous adipose tissue and serum (mean + SEM) of dairy cows. Adiposity Sampling Metabolite Low (LA) High (HA) SEM P Far off (FO) Close‐up (CU) Postpartum (PP) SEM P Serum free fatty acids (FFA) mEq/L FFA 0.43 0.63 0.05 &lt;0.01 0.27a 0.34b 0.98c 0.06 &lt;0.01 Serum fatty acids μmol/L Linoleic 341.5 222.6 78.8 NS 205.2 187 454 81.8 NS Arachidonic 42.2 20 10.5 0.02 22.2a 17.4a 53.8b 16.1 0.01 EPA 2.5 0.9 0.8 NS 0.7a 0.5a 2.7b 0.4 0.01 DHA 0.8 0.4 0.1 0.03 0.7 0.4 0.7 0.2 NS Adipose tissue fatty acids μmol/mg Linoleic acid 1340 1110 360 NS 1570 420 1720 500 NS Arachidonic acid 43.5 46.2 17 NS 43.9 9.3 52.4 16 NS EPA 0.83 0.43 0.3 NS 0.9 0.14 1.12 0.4 NS DHA 0.17 0.24 0.1 NS 0.23 0.31 0.07 0.2 NS Adipose tissue oxylipids nM/mg 9‐HODE 1.52 0.63 0.63 0.01 0.59 0.67 1.9 0.5 NS 9‐oxoODE 0.97 0.62 0.35 NS 0.49 1.01 0.87 0.26 NS 13‐HODE 2.42 0.71 0.84 0.05 0.77a 0.95a 2.97b 0.7 0.05 13‐oxoODE 0.62 0.62 0.47 NS 0.32 0.5 1.09 0.38 NS 5‐HETE 0.6 0.33 0.12 0.05 0.24a 0.56b 0.6b 0.12 0.05 11‐HETE 0.16 0.09 0.04 0.03 0.1a 0.08a 0.2b 0.04 0.04 15‐HETE 0.29 0.04 0.08 0.01 0.06a 0.12b 0.42c 0.08 0.01 20‐HETE 0.007 0.007 0.01 NS 0.007 0.007 0.006 0.004 NS Serum oxylipids nM/mL 9‐HODE 140.47 141.5 68.44 NS 210.98 111.45 101.65 60.4 NS 9‐oxoODE 82.3 67.6 36.76 NS 79.64a 87.41a 131b 41.3 0.02 13‐HODE 302 309.67 119.44 NS 364.14 301.73 252.77 98.5 NS 13‐oxoODE 31.97 19.18 2.09 NS 36.47 10.58 23.45 15.66 NS 5‐HETE 13.38 20.59 11.04 NS 12.62 29.75 5.55 10.58 NS 11‐HETE 8.65 7.98 4.69 NS 7.48 9.02 8.43 4.09 NS 15‐HETE 10.31 8.64 5.36 NS 10.72 11.8 5.82 4.87 NS 20‐HETE 26.45 28.45 1.7 NS 5.16 32.55 6.65 16.44 NS EPA=eicosapentaenoic acid; DHA=docosahexaenoic acid; HODE=hydroxyoctadecadienoic acid; oxoODE=oxooctadecadienoic acid; HETE= hydroxyeicosatetraenoic acid. Means in same row with different letter differ between sampling timepoint, P &lt; 0.05. NS= non‐significant effect, P &gt; 0.05.

Dietary chitosan affects metabolism of arachidonic acid in weaned piglets

The effects of chitosan on immune function via arachidonic acid (AA) pathway in weaned piglets were investigated. A total of 180 piglets (Duroc × Yorkshire × Landrace) were randomly assigned to 5 dietary treatments and fed a basal diet supplemented with 0 (control), 100, 500, 1000, and 2000 mg chitosan/kg feed, respectively. Results showed that serum AA, prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) contents in piglets were increased in a linear or quadratic dose-dependent manner with increasing chitosan on day 28 (P &amp;lt; 0.05). Chitosan increased serum cytosolic-phospholipase A2 (cPLA2) activity in a linear or quadratic dose-dependent manner on day 14 or 28, and improved 5-lipoxygenase (5-LOX) activity in a linear manner and cyclooxygenase-2 (COX-2) activity quadratically on day 28 (P &amp;lt; 0.05). Moreover, chitosan elevated gene expression of cPLA2 mRNA quadratically in the small intestine on days 14 and 28, increased the COX-2 mRNA expression in the duodenum or jejunum in a linear or quadratic manner on day 28, and improved the 5-LOX mRNA expression quadratically in the small intestine (P &amp;lt; 0.05). These results implied that the metabolism of AA was regulated by chitosan in a dose-dependent relationship, which may be one reason why chitosan affected immune function via AA pathway in weaned piglets.

Vitamin B-6 Status in Unsupplemented Pregnant Women Is Associated Positively with Serum Docosahexaenoic Acid and Inversely with the n–6-to-n–3 Fatty Acid Ratio

BackgroundVitamin B-6–deficient diets decrease plasma docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) concentrations in healthy adults. These fatty acids (FAs) are important for fetal neurodevelopment, but the relation between vitamin B-6 status and circulating polyunsaturated FAs (PUFAs) during pregnancy is unknown. ObjectiveWe sought to assess the relation between plasma pyridoxal 5′ phosphate (PLP; the active form of vitamin B-6) and serum DHA, EPA, AA, linoleic acid, eicosadienoic, and α-linolenic acid concentrations during pregnancy. MethodsA prospective cohort study in 186 healthy pregnant Brazilian women (aged 20–40 y) who were not using supplements was conducted in Rio de Janeiro, Brazil. Participants were enrolled in the first trimester of pregnancy (5–13 gestational weeks) and were followed up twice between 20–26 and 30–36 wk of gestation. Longitudinal linear mixed-effects regression models were used to evaluate the associations between 1) first-trimester PLP and PUFA concentrations across pregnancy and 2) ΔPLP (i.e., difference between third- and first-trimester plasma PLP concentrations) and PUFA concentrations across pregnancy. Models were adjusted for gestational week, first-trimester body mass index, smoking habit, and dietary intakes of vitamin B-6, fish, total fat, and PUFAs. ResultsPlasma PLP concentrations (median, IQR) substantially declined during pregnancy from 35.8 nmol/L (28.6–44.3 nmol/L) in the first trimester to 21.0 nmol/L (15.8–26.3 nmol/L) in the second trimester, and 16.8 nmol/L (12.9–20.3 nmol/L) in the third trimester (both P < 0.0001). Changes in plasma PLP concentrations across trimesters were positively associated with serum DHA concentrations (β = 0.252, P = 0.012) and inversely associated with serum n–6-to-n–3 (ω-6-to-ω-3) FA ratio (β = −0.010; P = 0.015), after adjustments for confounders. ConclusionsMaternal vitamin B-6 status during pregnancy was positively associated with the circulating concentration of DHA and inversely associated with n–6:n–3 FAs in Brazilian women who were not taking vitamin supplements. Further study is required to determine the impact of poor vitamin B-6 status on fetal neurodevelopment.

Effects of Low-Dose Pioglitazone on Serum Levels of Adiponectin, Dehydroepiandrosterone, Amyloid Beta Peptide, and Lipid Profile in Elderly Japanese People with Type 2 Diabetes

This study was performed to see how pioglitazone at low doses could affect blood biomarkers related to atherosclerosis and aging. The effects of an add-on treatment with pioglitazone (15 mg for males and 7.5 mg for females) for 6 months were assessed in 24 outpatients (12 males, 12 females) with type 2 diabetes aged ≥ 70 years. As doses of sulfonylurea were reduced in 10 patients, no significant differences in HbA1c and glucose levels were seen. After the treatment, serum levels of HDL cholesterol, arachidonic acid (predominant in males), and high-molecular-weight adiponectin significantly increased. The level of dehydroepiandrosterone sulfate significantly decreased. No significant changes were seen in those of small dense LDL cholesterol, high-sensitivity C-reactive protein, and amyloid beta peptides 1–40 and 1–42. There was a slight but significant increase in body weight, but apparent adverse effects were not observed. In conclusion, pioglitazone at low doses increased serum adiponectin, HDL cholesterol, and arachidonic acid levels but decreased serum dehydroepiandrosterone level, not associated with glycemia, in elderly Japanese people with type 2 diabetes. An optimal dose of pioglitazone should be sought for to minimize its adverse effects and to fully exert its pleiotropic effects such as antiatherosclerotic and antiaging effects.

Peroxidative metabolism of arachidonic acid in the course of Lyme arthritis.

The objective of the study was measurement of serum arachidonic acid level as well as the product of its peroxidation - 8-isoPGF2α, and the activity of phospholipase A2 and PAF-acetylhydrolase that participate in releasing 8-isoPGF2α from glycerol skeleton, and the potential designation of their role in the pathomechanism of Lyme disease (LD). Changes in the phospholipid arachidonic acid level and the level of 8-isoPGF2α were determined in the plasma and urine of patients with LA (n=57) and of healthy controls (n=41). The activity of phospholipase A2 and PAF acetylhydrolase were assayed. All examined parameters were also measured in the plasma of some LA patients (n=13) after antibiotics treatment. An almost 3-fold higher level of the total plasma 8-isoPGF2α was observed in LA patients compared to the controls, while in the urine it increased over 5-fold. The plasma PLA2 activity was more than 3-fold higher in LA patients than in the healthy subjects, while PAF acetylhydrolase activity was observed to be modestly, but not significantly lower. The total 8-isoPGF2α level in the plasma and urine of LA patients was significantly lower after antibiotics treatment. The plasma activity of PAF-AH in the LA patients was increased, while the cPLA2 activity decreased after antibiotics treatment. It may be suggested that in the course of LA, the level of binding 8-isoPGF2α is significantly enhanced, and it may also be suggested that uncontrolled changes in the lipid status of some patients may make their Lyme arthritis unresponsive to antibiotics.

Analysis of cytochrome P450 metabolites of arachidonic acid by stable isotope probe labeling coupled with ultra high-performance liquid chromatography/mass spectrometry

Cytochrome P450 metabolites of arachidonic acid (AA) belong to eicosanoids and are potent lipid mediators of inflammation. It is well-known that eicosanoids play an important role in numerous pathophysiological processes. Therefore, quantitative analysis of cytochrome P450 metabolites of AA, including hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatreinoic acids (EETs), and dihydroxyeicosatrienoic acids (DHETs) can provide crucial information to uncover underlying mechanisms of cytochrome P450 metabolites of AA related diseases. Herein, we developed a highly sensitive method to identify and quantify HETEs, EETs, and DHETs in lipid extracts of biological samples based on stable isotope probe labeling coupled with ultra high-performance liquid chromatography/mass spectrometry. To this end, a pair of stable isotope probes, 2-dimethylaminoethylamine (DMED) and d4-2-dimethylaminoethylamine (d4-DMED), were utilized to facilely label eicosanoids. The heavy labeled eicosanoid standards were prepared and used as internal standards for quantification to minimize the matrix and ion suppression effects in mass spectrometry analysis. In addition, the detection sensitivities of DMED labeled eicosanoids improved by 3–104 folds in standard solution and 5–138 folds in serum matrix compared with unlabeled analytes. Moreover, a good separation of eicosanoids isomers was achieved upon DMED labeling. The established method provided substantial sensitivity (limit of quantification at sub-picogram), high specificity, and broad linear dynamics range (3 orders of magnitude). We further quantified cytochrome P450 metabolites of AA in rat liver, heart, brain tissues and human serum using the developed method. The results showed that 19 eicosanoids could be distinctly detected and the contents of 11-, 15-, 16-, 20-HETE, 5,6-EET, and 14,15-EET in type 2 diabetes mellitus patients and 5-, 11-, 12-, 15-, 16-, 20-HETE, 8,9-EET, and 5,6-DHET in myeloid leukemia patients had significant changes, demonstrating that these eicosanoids may have important roles on the pathogenesis of type 2 diabetes mellitus and myeloid leukemia.