Adrenic Acid Research Articles

Lipid availability influences ferroptosis sensitivity in cancer cells by regulating polyunsaturated fatty acid trafficking.

Ferroptosis is a form of cell death caused by lipid peroxidation that is emerging as a target for cancer therapy, highlighting the need to identify factors that govern ferroptosis susceptibility. Lipid peroxidation occurs primarily on phospholipids containing polyunsaturated fatty acids (PUFAs). Here, we show that even though extracellular lipid limitation reduces cellular PUFA levels, lipid-starved cancer cells are paradoxically more sensitive to ferroptosis. Using mass spectrometry-based lipidomics with stable isotope fatty acid labeling, we show that lipid limitation induces a fatty acid trafficking pathway in which PUFAs are liberated from triglycerides to synthesize highly unsaturated PUFAs such as arachidonic and adrenic acid. These PUFAs then accumulate in phospholipids, including ether phospholipids, to promote ferroptosis sensitivity. Therefore, PUFA levels within cancer cells do not necessarily correlate with ferroptosis susceptibility. Rather, how cancer cells respond to extracellular lipid levels by trafficking PUFAs into proper phospholipid pools contributes to their sensitivity to ferroptosis.

Integrated metagenomics and metabolomics analyses revealed biomarkers in β-casein A2A2-type cows.

In Holstein cows, β-casein, one of the most critical proteins in milk, exists in two main genotypes, A1 and A2. Herein, 45 Holstein cows [categorized into three groups based on β-casein A1A1, A1A2, and A2A2 genotypes (N = 15)] with the same feeding management and litter size were enrolled to explore differences in rumen microflora and metabolites across various β-casein genotypes. Rumen fluids were collected for metagenomics and metabolomics analyses. Metabolomics and weighted gene co-expression network analysis (WGCNA) revealed that arachidonic acid (AA), adrenic acid (AdA), glycocholic acid (GCA), and taurocholic acid (TCA) were significantly and positively correlated with milk fat % in dairy cows (p < 0.05). Furthermore, macro-genomics and Spearman's correlation analysis revealed significant positive correlations (p < 0.05) between the characteristic flora (g_Acetobacter, g_Pseudoxanthomonas, g_Streptococcus, and g_Pediococcus) and the five characteristic metabolites in the rumen of A2A2 dairy cows. Moreover, functional enrichment analysis revealed more genes enriched to the TRP channel's inflammatory mediator-regulated pathway and the mTOR signaling pathway in A2A2 genotyped cows. Additionally, the regulatory effects of AA on bovine mammary epithelial cells (BMECs) were examined using CCK-8, EdU, and qRT-PCR assays, revealing that AA promoted triglyceride (TG) synthesis and upregulated the milk fat marker genes including SREBF1, ACSS2, AGPAT6, and FASN. Overall, we identified characteristic microorganisms and metabolites in A2A2 Holstein cows and established that AA could be a biomarker for higher milk fat %.

Effects of dietary supplementation with inactivated Lactobacillus plantarum on growth performance, haemato-biochemical parameters, liver fatty acids profile and intestinal microbiome of Nile tilapia.

This study investigated the effects of dietary supplementation with inactivated Lactobacillus plantarum for Nile tilapia (Oreochromis niloticus). Three treatments, in quintuplicate, were established: a control group, fish fed a diet without additives; LP group, fish fed a diet supplemented with live probiotic; and IP group, fish fed a diet supplemented with inactivated probiotic. Final weights (49.40 ± 3.15g) and weight gains (38.20 ± 3.23g) were increased in tilapia in the IP group. Feed conversion (1.32 ± 0.04) decreased significantly in the IP group. Haemato-biochemical parameters were significantly influenced by dietary supplementation. Erythrocyte count (262.74 ± 69.28 × 106 μL-1) was significantly low, while albumin (1.79 ± 1.12g dL-1) and cholesterol (254.14 ± 98.49mg dL-1) were high in the control group. Dietary supplementation modified the tilapia microbiome. Rhodobacter was abundant in fish intestines from the control and IP groups. Phreatobacter was abundant in the IP and LP groups, while Aurantimicrobium and Bosea were abundant in the LP group. Oleic acid (C18:1n9) was significantly increased in the LP (3.25 ± 0.49%) and IP (3.02 ± 0.30%) groups. Hexadecatrienoic acid (C16:3n4) was significantly increased (0.04 ± 0.01%) in the IP group, while Cis 11,14,17-eicosatrienoic acid (C20:3n3) (0.31 ± 0.03%) and adrenic acid (C22:4n6) (0.11 ± 0.02%) were significantly decreased in the LP group. Additionally, monounsaturated fatty acids (MUFA) were significantly increased (4.83 ± 0.35%) in the LP group compared to that in the control group. Collectively, these results indicate the potential of inactivated L. plantarum for use in commercial feed, leading to the conclusion that both inactivated and live L. plantarum can improve the Nile tilapia metabolism, altering haematological and biochemical markers.

Analysis of early-pregnancy metabolome in early- and late-onset gestational diabetes reveals distinct associations with maternal overweight.

It is not known whether the early-pregnancy metabolome differs in patients with early- vs late-onset gestational diabetes mellitus (GDM) stratified by maternal overweight. The aims of this study were to analyse correlations between early-pregnancy metabolites and maternal glycaemic and anthropometric characteristics, and to identify early-pregnancy metabolomic alterations that characterise lean women (BMI <25 kg/m2) and women with overweight (BMI ≥25 kg/m2) with early-onset GDM (E-GDM) or late-onset GDM (L-GDM). We performed a nested case-control study within the population-based prospective Early Diagnosis of Diabetes in Pregnancy cohort, comprising 210 participants with GDM (126 early-onset, 84 late-onset) and 209 normoglycaemic control participants matched according to maternal age, BMI class and primiparity. Maternal weight, height and waist circumference were measured at 8-14 weeks' gestation. A 2 h 75 g OGTT was performed at 12-16 weeks' gestation (OGTT1), and women with normal results underwent repeat testing at 24-28 weeks' gestation (OGTT2). Comprehensive metabolomic profiling of fasting serum samples, collected at OGTT1, was performed by untargeted ultra-HPLC-MS. Linear models were applied to study correlations between early-pregnancy metabolites and maternal glucose concentrations during OGTT1, fasting insulin, HOMA-IR, BMI and waist circumference. Early-pregnancy metabolomic features for GDM subtypes (participants stratified by maternal overweight and gestational timepoint at GDM onset) were studied using linear and multivariate models. The false discovery rate was controlled using the Benjamini-Hochberg method. In the total cohort (n=419), the clearest correlation patterns were observed between (1) maternal glucose concentrations and long-chain fatty acids and medium- and long-chain acylcarnitines; (2) maternal BMI and/or waist circumference and long-chain fatty acids, medium- and long-chain acylcarnitines, phospholipids, and aromatic and branched-chain amino acids; and (3) HOMA-IR and/or fasting insulin and L-tyrosine, certain long-chain fatty acids and phospholipids (q<0.001). Univariate analyses of GDM subtypes revealed significant differences (q<0.05) for seven non-glucose metabolites only in overweight women with E-GDM compared with control participants: linolenic acid, oleic acid, docosapentaenoic acid, docosatetraenoic acid and lysophosphatidylcholine 20:4/0:0 abundances were higher, whereas levels of specific phosphatidylcholines (P-16:0/18:2 and 15:0/18:2) were lower. However, multivariate analyses exploring the early-pregnancy metabolome of GDM subtypes showed differential clustering of acylcarnitines and long-chain fatty acids between normal-weight and overweight women with E- and L-GDM. GDM subtypes show distinct early-pregnancy metabolomic features that correlate with maternal glycaemic and anthropometric characteristics. The patterns identified suggest early-pregnancy disturbances of maternal lipid metabolism, with most alterations observed in overweight women with E-GDM. Our findings highlight the importance of maternal adiposity as the primary target for prevention and treatment.

Iron(III)-salophene catalyzes redox cycles that induce phospholipid peroxidation and deplete cancer cells of ferroptosis-protecting cofactors

Ferroptosis, a lipid peroxidation-driven cell death program kept in check by glutathione peroxidase 4 and endogenous redox cycles, promises access to novel strategies for treating therapy-resistant cancers. Chlorido [N,N′-disalicylidene-1,2-phenylenediamine]iron (III) complexes (SCs) have potent anti-cancer properties by inducing ferroptosis, apoptosis, or necroptosis through still poorly understood molecular mechanisms. Here, we show that SCs preferentially induce ferroptosis over other cell death programs in triple-negative breast cancer cells (LC50 ≥ 0.07 μM) and are particularly effective against cell lines with acquired invasiveness, chemo- or radioresistance. Redox lipidomics reveals that initiation of cell death is associated with extensive (hydroper)oxidation of arachidonic acid and adrenic acid in membrane phospholipids, specifically phosphatidylethanolamines and phosphatidylinositols, with SCs outperforming established ferroptosis inducers. Mechanistically, SCs effectively catalyze one-electron transfer reactions, likely via a redox cycle involving the reduction of Fe(III) to Fe(II) species and reversible formation of oxo-bridged dimeric complexes, as supported by cyclic voltammetry. As a result, SCs can use hydrogen peroxide to generate organic radicals but not hydroxyl radicals and oxidize membrane phospholipids and (membrane-)protective factors such as NADPH, which is depleted from cells. We conclude that SCs catalyze specific redox reactions that drive membrane peroxidation while interfering with the ability of cells, including therapy-resistant cancer cells, to detoxify phospholipid hydroperoxides.

Low serum adrenic acid levels in infants and subsequent food-induced anaphylaxis

BackgroundThe dietary fat hypothesis links increases in allergic diseases to reduced consumption of n-3 polyunsaturated fatty acids (PUFAs) from fish, e.g., eicosapentaenoic acid (EPA), and increased intake of n-6 PUFAs from vegetable oils, e.g., arachidonic acid (AA). ObjectiveBuilding upon the 'fat hypothesis', we aimed to investigate the association between 24 types of serum fatty acid levels in infants and the risk of subsequent food-induced anaphylaxis (FIA) by 2 years of age as the primary outcome. MethodsThis study was conducted as a prespecified supplemental analysis within the ABC randomized clinical trial. We measured levels of 24 fatty acids in residual serum samples collected from 268 infants at 5-6 months of age using gas chromatography-mass spectrometry. ResultsAmong the 258 infants, 58 exhibited immediate-type food allergies, while 200 showed no food allergy (NFA). Of the 58 infants, 12 were diagnosed with FIA, while the remaining 46 had non-anaphylactic food allergy (NAFA). Unexpectedly, among the 24 fatty acids, only adrenic acid (AdA), also known as docosatetraenoic acid, which is one of the n-6 PUFAs, showed significantly lower levels in infants with FIA (median [IQR] (wt.%): 0.16 [0.14-0.17]), compared to those with NFA (0.19 [0.17-0.21]) (P=.0007). In contrast, AdA levels in infants with NAFA were 0.19 [0.16-0.21] (wt.%), which did not differ significantly from infants with NFA (P=.69). ConclusionThis study generated a hypothesis suggesting that infants with low serum AdA levels might be at greater risk of subsequent FIA. This unexpected result warrants further investigation.

Liver phospholipid fatty acid composition in response to chronic high-fat diets

Liver phospholipid fatty acid composition depends on the dietary lipid intake and the efficiency of hepatic enzymatic activity. Our study aimed to simultaneously investigate the liver phospholipid fatty acid composition in response to chronic linseed, palm, or sunflower oil diets. We used adult female C57/BL6 mice and randomly divided them into control and three groups treated with 25 % dietary oils. Prior to treatment, we analyzed the fatty acid profiles in dietary oils and hepatocytes and, after 100 days, the fatty acid composition in the liver using gas-liquid chromatography. Linseed oil treatment elevated alpha-linolenic, eicosapentaenoic, and docosapentaenoic acids and reduced arachidonic and docosatetraenoic acids, consequently lowering the n-6/n-3 ratio. Palm oil treatment increased linoleic acid and decreased docosahexaenoic acid, contributing to an elevated n-6/n-3 ratio. Sunflower oil treatment elevated total monounsaturated fatty acids by increasing palmitoleic, oleic, and vaccenic acids. The estimated activity of Δ9 desaturase was significantly elevated in the sunflower oil group, while Δ5 desaturase was the highest, and Δ6 desaturase was the lowest after the linseed oil diet. Our findings demonstrate that chronic consumption of linseed, palm, or sunflower oil alters the distribution of liver phospholipid fatty acids differently. Sunflower oil diet elevated total monounsaturated fatty acids, proposing potential benefits for liver tissue health. Considering these outcomes, a substantial recommendation emerges to elevate linseed oil intake, recognized as the principal ALA source, thereby aiding in reducing the n-6/n-3 ratio. Moreover, modifying dietary habits to incorporate specific vegetable oils in daily consumption could substantially enhance overall health.

Association of serum fatty acid pattern with depression in U.S. adults: analysis of NHANES 2011–2012

BackgroundExposure to different concentration levels of fatty acids (FAs) may have an impact on depression. However, previous studies using individual FAs may not reflect the performance of mixtures of various FAs, and the associations of FA patterns with depression remain unclear.MethodsWe conducted the cross-sectional analysis in 792 adults aged 18 and older with available serum FAs and depression screening data in the National Health and Nutrition Examination Survey (NHANES) 2011–2012. The serum concentrations of thirty FAs were measured using gas chromatography-mass spectrometry and their percentage compositions were subsequently calculated. Depression was defined as the Patient Health Questionnaire-9 score ≥ 10. We employed principal component analysis to derive serum FA patterns. We examined the association between these patterns and depression in the overall population and various subgroups through survey-weighted logistic regression.ResultsFour distinct patterns of serum FAs were identified: ‘high eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); low docosatetraenoic acid (DTA) and docosapentaenoic acid (DPA) n-6’, ‘high long-chain saturated FA and long chain FA’, ‘low median-chain saturated FA and myristoleic acid’ and ‘low capric acid and lauric acid; high gamma-linolenic acid (GLA) and stearidonic acid (SDA)’ pattern. Individuals in the high tertile of ‘high EPA and DHA; low DTA and DPA n-6’ pattern score had 0.46 (95% CI: 0.22, 0.93) lower odds of developing depression compared to individuals in the lowest tertile after adjusting for confounders such as age, sex, physical activity and total energy intake, etc. The odds ratio (OR) of depression was increased in the population with the highest tertile of ‘low capric acid and lauric acid; high GLA and SDA’ pattern (OR: 2.45, 95% CI: 1.24, 4.83). In subgroup analyses, we observed that the association between ‘high EPA and DHA; low DTA and DPA n-6’ and depression persisted among specific demographic and lifestyle subgroups, including females, non-Mexican Americans, non-obese, those aged over 60 years, smokers and drinkers. Similarly, ‘low capric acid and lauric acid; high GLA and SDA’ showed stable associations in female, non-Mexican Americans and smokers.ConclusionsSerum FA patterns are associated with depression, and their relationships vary across sex, race, BMI, age, smoking and drinking subgroups, highlighting the importance of considering specific FA patterns within these demographic and lifestyle categories. Utilization of combined FA administration may serve as a mitigation measure against depression in these specific populations.

Metabolic Analysis and Renal Protective Effects of Linagliptin and Empagliflozin in Alport Syndrome.

We previously demonstrated that Empagliflozin (Empa), a sodium-glucose cotransporter-2 (SGLT2) inhibitor, reduces intrarenal lipid accumulation and slows kidney function decline in experimental Alport syndrome (AS). In this study, we aimed to evaluate the renal protective benefits of Linagliptin (Lina), a dipeptidyl peptidase-4 (DPP4) inhibitor in AS and compare it to Empa. Metabolite distribution in kidney cortices was assessed using mass spectrometry imaging. We examined albuminuria and histological changes in kidneys from AS mice treated with Lina and/or Empa or vehicle. Several metabolites, including adrenic acid (AdA) and glucose, were increased in renal cortices of AS mice when compared to wildtype (WT) mice, while eicosapentaenoic acid (EPA) levels were decreased. In addition, a redistribution of AdA from the glomerular compartment in WT mice to the tubulointerstitial compartment in AS mice was observed. Both Lina and Empa treatments were found to reduce albuminuria, to extend the survival of AS mice for about 10 days, and to decrease glomerulosclerosis and tubulointerstitial fibrosis compared to WT mice. There were no significant differences with regard to the renal phenotype observed between Empa and Lina treated AS mice, and the combination of Lina and Empa was not superior to individual treatments. In vitro experiments revealed that DPP4 is expressed in podocytes and tubular cells derived from both AS and WT mice. Differently from what we have reported for Empa, Lina treatment was found to reduce glucose-driven respiration in AS tubular cells, but not in AS podocytes. Renal expression patterns and spatial distribution of several metabolites differ in AS compared to WT mice. While Lina and Empa treatments similarly partially slow the progression of kidney disease in AS, the metabolic mechanisms conferring the protective effect may be different.

Mechanism of the components compatibility of Scutellariae Radix and Coptidis Rhizoma on mice with hyperlipidemia by regulating the Cyp4a family

Ethnopharmacological relevanceScutellaria baicalensis Georgi (Scutellariae Radix, SR) and Coptis chinensis Franch (Coptidis Rhizoma, CR) is a classic herbal pair used in many Traditional Chinese Medicine formulations in the treatment of hyperlipidemia (HLP). As effective ingredients of the drug pair, the effects and mechanisms of berberine and baicalin in the treatment of HLP in the form of components compatibility are still unclear. Aim of the studyTo explore the mechanism of the components compatibility of SR and CR in the treatment of HLP. Materials and methodsThe HLP model was established by a high-fat diet. Serum biochemical indexes were detected. Transcriptomics and metabolomics were detected. RT-PCR and Western Blot were used to analyze the effect of RA on the expression of the Cyp4a family during the treatment of HLP. ResultsBerberine-baicalin (RA) has a good effect in the treatment of HLP. RA can significantly reduce the body weight and liver weight of HLP, reduce the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), and increase the level of high-density lipoprotein (HDL-C). Through transcriptomic analysis, RA significantly reversed the gene expression of Cyp4a10, Cyp4a12 b, Cyp4a31, and Cyp4a32 in cytochrome P450 family 4 subfamily a (Cyp4a) which related to fatty acid degradation in the liver of HLP mice. The results of fatty acid detection showed that RA could significantly regulate heptanoic acid, EPA, adrenic acid, DH-γ-linolenic acid, and DPA in the cecum of HLP mice. The Cyp4a family genes regulated by RA are closely related to a variety of fatty acids regulated by RA. RT-PCR confirmed that RA could regulate Cyp4a mRNA expression in HLP mice. WB also showed that RA can regulate the protein expression level of Cyp4a. ConclusionThe components compatibility of SR and CR can effectively improve the blood lipid level of HLP mice, its mechanism may be related to regulating Cyp4a gene expression and affecting fatty acid degradation, regulating the level of fatty acid metabolism in the body.

Association of Human Milk Fatty Acid Composition with Maternal Cardiometabolic Diseases: An Exploratory Prospective Cohort Study.

Background: Human milk fatty acids derive from maternal diet, body stores, and mammary synthesis and may reflect women's underlying cardiometabolic health. We explored whether human milk fatty acid composition was associated with maternal cardiometabolic disease (CMD) during pregnancy and up to 5 years postpartum. Materials and Methods: We analyzed data from the prospective CHILD Cohort Study on 1,018 women with no preexisting CMD who provided breast milk samples at 3-4 months postpartum. Milk fatty acid composition was measured using gas-liquid chromatography. Maternal CMD (diabetes or hypertension) was classified using questionnaires and birth records as no CMD (reference outcome group; 81.1%), perinatal CMD (developed and resolved during the perinatal period; 14.9%), persistent CMD (developed during, and persisted beyond, the perinatal period; 2.9%), and incident CMD (developed after the perinatal period; 1.1%). Multinomial logistic regression was used to model associations between milk fatty acid composition (individual, summary, ratios, and patterns identified using principal component analysis) and maternal CMD, adjusting for pre-pregnancy anthropometry and race/ethnicity. Results: Medium-chain saturated fatty acids (MC-SFA), lauric (C12:0; odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.60-0.89) and myristic acid (C14:0; OR = 0.80, 95% CI = 0.66-0.97), and the high MC-SFA principal component pattern (OR = 0.86, 95% CI = 0.76-0.96) were inversely associated with perinatal CMD. Long-chain polyunsaturated fatty acids adrenic acid (C22:4n-6) was positively associated with perinatal (OR = 1.21, 95% CI = 1.01-1.44) and persistent CMD (OR = 1.56, 95% CI = 1.08-2.25). The arachidonic (C20:4n-6)-to-docosahexaenoic acid (C22:6n-3) ratio was inversely associated with incident CMD (OR = 0.52, 95% CI = 0.28-0.96). Conclusions: These exploratory findings highlight a potential novel utility of breast milk for understanding women's cardiometabolic health.

Maternal plasma phospholipid polyunsaturated fatty acids in early pregnancy and thyroid function throughout pregnancy: a longitudinal study

BackgroundEvidence has indicated that polyunsaturated fatty acids (PUFAs)-enriched diet could reduce inflammation because of thyroid autoimmunity in vivo, and therefore, enhance thyroid function. ObjectivesWe investigated whether early pregnancy plasma phospholipid PUFAs could benefit maternal thyroid function across pregnancy, which is critical to fetal brain development and growth in pregnancy. MethodsWithin the National Institute of Child Health and Human Development Fetal Growth Studies–Singleton Cohort, we collected plasma samples longitudinally from 214 subjects [107 with gestational diabetes mellitus (GDM) matched with 107 controls] with a singleton pregnancy. We measured 11 PUFAs at early pregnancy (10–14 wk) and 5 thyroid biomarkers at 10–14, 15–26, 23–31, and 33–39 wk, including free thyroxine (fT4), free triiodothyronine (fT3), thyroid-stimulating hormone, antithyroid peroxidase, and antithyroglobulin. Associations of PUFAs with thyroid function biomarkers and relative risk (RR) of gestational hypothyroidism (GHT) during pregnancy were assessed using generalized linear mixed models and modified Poisson regression, respectively. ResultsAfter sample weighting because of subjects with GDM over-representing in the analytic sample with biomarkers, eicosapentaenoic acid (EPA) at early pregnancy was associated with a reduction of 0.24 pmol/L (95% confidence intervals: −0.31, −0.16) in fT3 across gestation per standard deviation (SD) increment, whereas docosahexaenoic acid (DHA) at early pregnancy was associated with an increment of 0.04 ng/dL (0.02, 0.05) in fT4 across gestation per SD increment. Furthermore, EPA and docosatetraenoic acid (DTA) were associated with lower risks of persistent GHT (EPA—RR: 0.13; 0.06, 0.28; DTA—RR: 0.24; 0.13, 0.44) per SD increment. All significant associations remained robust in sensitivity analysis and multiple testing. ConclusionsCertain plasma phospholipid PUFAs were associated with optimal levels of thyroid biomarkers and even lower risk of GHT throughout pregnancy, which might be potentially targeted for maternal thyroid regulation in early pregnancy. Clinical Trial RegistryThis trial was registered at https://beta.clinicaltrials.gov/study/NCT00912132?distance=50&term=NCT00912132&rank=1 as NCT00912132.

Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations in Chronic Pancreatitis: A Multicenter, Cross-Sectional Study.

Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations. NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear cells (PBMCs) from controls (n = 16), AP/RAP (n = 17), and CP (n = 15) were measured by cytometry by time-of-flight. Plasma NGAL was elevated in subjects with CP compared with controls (area under the curve [AUC] = 0.777) or AP/RAP (AUC = 0.754) in univariate and multivariate analyses with sex, age, body mass index, and smoking (control AUC = 0.874; AP/RAP AUC = 0.819). NGAL was elevated in CP and diabetes compared with CP without diabetes ( P < 0.001). NGAL + PBMC populations distinguished CP from controls (AUC = 0.950) or AP/RAP (AUC = 0.941). Linoleic acid was lower, whereas dihomo-γ-linolenic and adrenic acids were elevated in CP ( P < 0.05). Linoleic acid was elevated in CP with diabetes compared with CP subjects without diabetes ( P = 0.0471). Elevated plasma NGAL and differences in NGAL + PBMCs indicate an immune response shift that may serve as biomarkers of CP. The potential interaction of FAs and NGAL levels provide insights into the metabolic pathophysiology and improve diagnostic classification of CP.

Regulatory effects of tea polysaccharides on hepatic inflammation, gut microbiota dysbiosis, and serum metabolomic signatures in beef cattle under heat stress.

Long-term heat stress (HS) severely restricts the growth performance of beef cattle and causes various health problems. The gut microbiota plays a crucial role in HS-associated inflammation and immune stress involving lymphocyte function. This study investigated the effects of dietary tea polysaccharide (TPS), a natural acidic glycoprotein, on HS-induced anorexia, inflammation, and gut microbiota dysbiosis in Simmental beef cattle. The cattle were divided into two groups, receiving either normal chow or normal chow plus TPS (8g/kg, 0.8%). Transcriptome sequencing analysis was used to analysis the differential signaling pathway of liver tissue. 16S rDNA sequencing was performed to analysis gut microbiota of beef cattle. Serum metabolite components were detected by untargeted metabolomics analysis. Hepatic transcriptomics analysis revealed that differentially expressed genes in TPS-fed cattle were primarily enriched in immune processes and lymphocyte activation. TPS administration significantly reduced the expression of the TLR4/NF-κB inflammatory signaling pathway, alleviating HS-induced hepatic inflammation. Gut microbiota analysis revealed that TPS improved intestinal homeostasis in HS-affected cattle by increasing bacterial diversity and increasing the relative abundances of Akkermansia and Alistipes while decreasing the Firmicutes-to-Bacteroidetes ratio and the abundance of Agathobacter. Liquid chromatography-tandem mass spectrometry (LC‒MS/MS) analysis indicated that TPS significantly increased the levels of long-chain fatty acids, including stearic acid, linolenic acid, arachidonic acid, and adrenic acid, in the serum of cattle. These findings suggest that long-term consumption of tea polysaccharides can ameliorate heat stress-induced hepatic inflammation and gut microbiota dysbiosis in beef cattle, suggesting a possible liver-gut axis mechanism to mitigate heat stress.

Fatty acids profile in pregnancies affected by neural tube defects

Abstract This study aimed to determine if maternal fatty acids (FA) levels during pregnancy are associated with the occurrence of neural tube defects (NTDs) and to explore the correlation between FA and maternal vitamin D, homocysteine, vitamin B12, and folate in cases. Plasma FA composition was assessed using capillary gas chromatography. Comparisons between cases and controls were performed by independent samples t-test for continuous variables. Cases had significantly higher levels of heptadecanoic acid, linolelaidic acid, and arachidonic acid (ARA):(eicosapentaenoic acid+docosahexaenoic acid) ratio than controls (p &lt; 0.05). Nervonic acid, ARA, adrenic acid, eicosapentaenoic acid, docosahexaenoic acid, and omega-3 polyunsaturated fatty acids (n-3 PUFA) levels were significantly lower in cases (p &lt; 0.05). Maternal 25-hydroxyvitamin D (25(OH)D) levels were positively correlated with maternal polyunsaturated fatty acids and omega-6 polyunsaturated fatty acids. RBC folate levels were negatively correlated with n-3 PUFA. Further research is required to clarify the association of FA metabolism with NTDs.

Serum metabolomics characteristics and fatty-acid-related mechanism of cirrhosis with histological response in chronic hepatitis B.

Background and aims: The serum metabolites changes in patients with hepatitis B virus (HBV)-related cirrhosis as progression. Peroxisome proliferator-activated receptor gamma (PPARγ) is closely related to lipid metabolism in cirrhotic liver. However, the relationship between fatty acids and the expression of hepatic PPARγ during cirrhosis regression remains unknown. In this study, we explored the serum metabolic characteristics and expression of PPARγ in patients with histological response to treatment with entecavir. Methods: Sixty patients with HBV-related cirrhosis were selected as the training cohort with thirty patients each in the regression (R) group and non-regression (NR) group based on their pathological changes after 48-week treatment with entecavir. Another 72 patients with HBV-related cirrhosis and treated with entecavir were collected as the validation cohort. All of the serum samples were tested using ultra-performance liquid chromatography coupled to tandem mass spectrometry. Data were processed through principal component analysis and orthogonal partial least square discriminant analysis. Hepatic PPARγ expression was observed using immunohistochemistry. The relationship between serum fatty acids and PPARγ was calculated using Pearson's or Spearman's correlation analysis. Results: A total of 189 metabolites were identified and 13 differential metabolites were screened. Compared to the non-regression group, the serum level of fatty acids was higher in the R group. At baseline, the expression of PPARγ in hepatic stellate cells was positively correlated with adrenic acid (r 2 = 0.451, p = 0.046). The expression of PPARγ in both groups increased after treatment, and the expression of PPARγ in the R group was restored in HSCs much more than that in the NR group (p = 0.042). The adrenic acid and arachidonic acid (AA) in the R group also upgraded more than the NR group after treatment (p = 0.037 and 0.014). Conclusion: Baseline serum differential metabolites, especially fatty acids, were identified in patients with HBV-related cirrhosis patients who achieved cirrhosis regression. Upregulation of adrenic acid and arachidonic acid in serum and re-expression of PPARγ in HSCs may play a crucial role in liver fibrosis improvement.

METABOLOMIC PROFILES OF DEMENTIA RISK AND MOBILITY DECLINE IN A BIRACIAL COHORT OF OLDER ADULTS

Abstract Age-related mobility decline precedes future cognitive impairment and dementia. Blood biomarkers underlying this connection are less clear. This study aims to examine metabolomic profiles of dementia risk and mobility decline in the Health, Aging and Body Composition Study. Dementia diagnosis was determined by race-specific decline in Modified Mini-Mental State Examination scores, medication use, and hospital records. 2450 participants were free of dementia at year 2 and had 613 targeted plasma metabolites. 534(22%) developed dementia during a mean follow-up of 9.3(SD=4.1) years. 2028 participants had repeated 20-meter usual gait speed up to 10 years follow-up. We performed Cox regression and linear regression with LASSO models to determine which metabolites would predict dementia risk and gait speed decline, respectively. After adjustment for age, sex, race, and education, 30 metabolites were significant predictors of incident dementia. Top-ranked metabolites included glyceric acid, niacinamide, androsterone 3- glucuronide, phosphatidylcholine (P-34:4)/PC(O-34:5), aminobutyric acid, xanthine, sphingomyelin (d18:1/14:0) (hazard ratios&amp;lt; 1), suberic acid, lysophosphatidylethanolamine (18:1), threitol, and andrenic acid (hazard ratios&amp;gt;1). These metabolites were enriched in arginine biosynthesis, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism and arginine and proline metabolism(p&amp;lt; 0.05). Of these metabolites, threitol, sphingomyelin (d18:1/14:0), adrenic acid, and phosphatidylethanolamine (P-36:0)/PE(O-36:1) were also significant predictors of mobility decline in a consistent direction. This longitudinal study reveals unique and shared metabolomic risk profiles for dementia and mobility decline. Several metabolites in amino-acid pathways and urea may be important in the development of dementia and certain sugar and lipids with long-chain and very long-chain fatty acids also predict mobility decline.

Effects of dietary Chinese herbal mixtures on productive performance, egg quality, immune status, caecal and offspring meconial microbiota of Wenchang breeder hens.

This study aimed to evaluate the effects of Chinese herbal mixtures (CHMs) on productive performance, egg quality, immune status, anti-apoptosis ability, caecal microbiota, and offspring meconial microbiota in hens. A total of 168 thirty-week-old Wenchang breeder hens were randomly divided into two groups, with each group comprising six replicate pens of fourteen hens. The groups were fed a basal diet (CON group) and a basal diet with 1,000 mg/kg CHMs (CHMs group) for 10 weeks. Our results showed that dietary supplementation with CHMs increased the laying rate, average egg weight, hatch of fertile, and offspring chicks' weight while concurrently reducing the feed conversion ratio (FCR) and embryo mortality (p < 0.05). The addition of CHMs resulted in significant improvements in various egg quality parameters, including eggshell strength, albumen height, haugh unit, and the content of docosatetraenoic acid (C20:4n-6) in egg yolk (p < 0.05). The supplementation of CHMs had a greater concentration of IgA and IgG while decreasing the content of IL-6 in serum compared with the CON group (p < 0.05). Addition of CHMs to the diet increased the expression of Bcl-2 and IL-4 in liver and ovary, decreased the expression of IL-1β, Bax, and Caspase-8 in jejunum and ovary, and decreased the expression of NF-κB in liver, jejunum, and ovary (p < 0.05). Moreover, dietary CHMs reduced the abundance of Desulfovibrio in caecal microbiota as well as decreased the abundance of Staphylococcaceae_Staphylococcus and Pseudomonadaceae_Pseudomonas in the offspring meconial microbiota (p < 0.05). In conclusion, the CHMs could improve productive parameters by enhancing immune status, anti-apoptosis capacity, and modulating the caecal microbiota of Wenchang breeder hens, as well as maintaining the intestinal health of the offspring chicks.

Alginate oligosaccharide extends the service lifespan by improving the sperm metabolome and gut microbiota in an aging Duroc boars model.

Alginate oligosaccharide (AOS), as a natural non-toxic plant extract, has been paid more attention in recent years due to its strong antioxidant, anti-inflammatory, and even anti-cancer properties. However, the mechanism by which AOS affects animal reproductive performance is still unclear. The purpose of this study is to use multi-omics technology to analyze the effects of AOS in extending the service lifespan of aging boars. The results showed that AOS can significantly improve the sperm motility (p < 0.05) and sperm validity rate (p < 0.001) of aging boars and significantly reduce the abnormal sperm rate (p < 0.01) by increasing the protein levels such as CatSper 8 and protein kinase A (PKA) for semen quality. At the same time, AOS significantly improved the testosterone content in the blood of boars (p < 0.01). AOS significantly improved fatty acids such as adrenic acid (p < 0.05) and antioxidants such as succinic acid (p < 0.05) in sperm metabolites, significantly reducing harmful substances such as dibutyl phthalate (p < 0.05), which has a negative effect on spermatogenesis. AOS can improve the composition of intestinal microbes, mainly increasing beneficial bacteria Enterobacter (p = 0.1262) and reducing harmful bacteria such as Streptococcus (p < 0.05), Prevotellaceae_UCG-001 (p < 0.05), and Prevotellaceae_NK3B31_group (p < 0.05). Meanwhile, short-chain fatty acids in feces such as acetic acid (p < 0.05) and butyric acid (p < 0.05) were significantly increased. Spearman correlation analysis showed that there was a close correlation among microorganisms, sperm metabolites, and sperm parameters. Therefore, the data indicated that AOS improved the semen quality of older boars by improving the intestinal microbiota and sperm metabolome. AOS can be used as a feed additive to solve the problem of high elimination rate in large-scale boar studs.

Abstract 14625: Association of Eicosanoid Metabolites With Cardiac Structure and Function

Introduction: Eicosanoids are bioactive lipids that govern the upstream initiation of pro- and anti-inflammatory activity. They may serve as important pathways by which obesity and cardiometabolic disease lead to the development of heart failure with preserved ejection fraction (HFpEF). Objective: We sought to examine the association of plasma circulating eicosanoid metabolites with subclinical cardiac remodeling as ascertained by cardiac magnetic resonance imaging (CMR) as important determinants of HFpEF risk. Methods: We studied 3880 MESA study participants (mean age 63±10 years, 53% women) who underwent plasma metabolite profiling using a mass spectrometry-based platform and CMR. We used multivariable linear regression to examine the association of eicosanoid metabolites with left ventricular mass index (LVMI, primary outcome), LV end-diastolic volume index (LVEDV), and left atrial volume (LAV). Results: Of 811 eicosanoids, 158 were associated with LVMI (Figure; FDR q &lt;0.05 for all). Specifically, derivatives of eicosadienoic acid (15 oxoEDE), linoleic acid (9,10 diHOME), and arachidonic acid (12(R) HETE) were negatively associated with LVMI and prostaglandin 19R-hydroxy-PGE1 was positively associated with LVMI. Of 158 metabolites, 65 were are also associated with LVEDV including derivatives of linoleic acid (13(S) HOTrE), oxylipin 11-HETE and 15 oxoEDE. Of 158 metabolites, Adrenic acid is also associated with LAV. Conclusions: We found that specific eicosanoids including 15 oxoEDE, 9,10 diHOME, and 12(R) HETE were associated with LVMI, an important measure of subclinical cardiac remodeling and precursor to HFpEF. As causal drivers of HFpEF are poorly characterized, a better understanding of pro- and anti-inflammatory eicosanoid pathways that contribute to cardiac remodeling may have important implications for the prevention of HFpEF.