Adrenic Acid Research Articles

Hepatocyte-specific deletion of thromboxane-prostanoid receptor has protective effects on alcohol-associated liver disease

Alcohol-associated liver disease (ALD) is a major health issue worldwide with limited effective treatment options. Thromboxane-prostanoid receptor (TP-R), a G-protein-coupled receptor, is widely expressed in liver. Previous studies reported that an alcohol diet increased levels of TP-R ligands, thromboxane A2 and 8-isoprostane, in mouse liver. However, the role of TP-R signaling in ALD still remains unknown. Here, to test the hypothesis that deleting hepatocyte TP-R ameliorates liver injury caused by an alcohol diet, nine-week female hepatocyte-specific TP-R knock-out mice (KO) and their wild-type (WT) littermate control mice were fed the Lieber-DeCarli control (CONT) or 5% (v/v) ethanol (ET) diet for 4 weeks. Mice were divided into four groups: WT-CONT (n=8), KO-CONT (n=8), WT-ET (n=10), and KO-ET (n=8). Real-time PCR analyses showed that deleting hepatocyte TP-R attenuated alcohol-induced increase in mRNA levels of inflammatory markers including interleukin 6 ( P<0.01) and lipocalin 2 ( P<0.01). In addition, mRNA levels of other inflammatory markers including C-C motif chemokine ligand 2 ( P<0.05) and interleukin 1β ( P<0.01) were increased significantly only in WT-ET mice but not in KO-ET mice compared with controls. Of note, both real-time PCR and immunohistochemistry analyses showed that deleting TP-R in hepatocytes attenuates alcohol-induced increase in the expression of cluster of differentiation 36 (CD36, P<0.05), a fatty acid transport protein. Previous studies documented that chronic alcohol consumption led to hepatic steatosis through promoting CD36-mediated fatty acid uptake. Interestingly, the gas chromatographic analysis of liver lipids revealed a remarkable increase in linoleic acid ( P<0.05) level in liver triglyceride (TG) in WT-ET mice and this effect was blunted in KO-ET group. Additionally, the alcohol diet increased the levels of arachidonic acid ( P<0.01), dihomo-gamma-linoleic acid ( P<0.05), and docosatetraenoic acid ( P<0.05) in liver TG of WT mice, but these fatty acids were not altered by alcohol diet in KO-ET group. Chronic alcohol feeding is known to elicit an oxidative stress in mouse livers though increasing the activity of cytochrome P450 family 2 subfamily E member 1 (CYP2E1). Accordingly, we noted that ablation of hepatocyte TP-R inhibited liver CYP2E1 activity in mice fed an alcohol diet ( P<0.01). Moreover, the alcohol diet increased liver malondialdehyde level in WT mice ( P<0.01) but not in KO mice. These findings suggest that hepatocyte TP-R plays an important role in regulating lipid metabolism and oxidative stress, thereby contributing to the development of AALD. This study was supported by R21 awards from NIH-National Institute on Alcohol Abuse and Alcoholism (R21- AA025445 and R21-AA027367) and a Merit Award from the Department of Veterans Affairs (I01CX002084). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The predictive value of chest computed tomography images, tumor markers, and metabolomics in the identification of benign and malignant pulmonary nodules.

Invasive puncture biopsy is currently the main method of identifying benign and malignant pulmonary nodules (PNs). This study aimed to investigate the application effect of chest computed tomography (CT) images, tumor markers (TMs), and metabolomics in the identification of benign and malignant PNs (MPNs). A total of 110 patients with PNs who were hospitalized in Dongtai Hospital of Traditional Chinese Medicine from March 2021 to March 2022 were selected as the study cohort. A retrospective analysis study of chest CT imaging, serum TMs testing, and plasma fatty acid (FA) metabolomics was performed on all participants. According to the pathological results, participants were divided into a MPN group (n=72) and a benign PN (BPN) group (n=38). The morphological signs of CT images, the levels and positive rate of serum TMs, and the plasma FA indicator were compared between groups. There were significant differences between the MPN group and the BPN group in the CT morphological signs, including location of PN and the number of patients with or without lobulation sign, spicule sign, and vessel convergence sign (P<0.05). Serum carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), and squamous cell carcinoma antigen (SCC-Ag) were not significantly different between the 2 groups. The serum contents of CEA and CYFRA 21-1 in the MPN group were remarkably higher than those in the BPN group (P<0.05). The plasma levels of palmitic acid, total omega-3 polyunsaturated FA (W3), nervonic acid, stearic acid, docosatetraenoic acid, linolenic acid, eicosapentaenoic acid, total saturated FA, and total FA were much higher in the MPN group than the BPN group (P<0.05). In conclusion, chest CT images and TMs, combined with metabolomics, has a good application effect in the diagnosis of BPNs and MPNs, and is worthy of further promotion.

Precursors of specialized pro-resolving mediators (SPMs) are decreased in hypertension, and treatment with SPMs improve vascular relaxation via formyl peptide-receptor-2

Specialized pro-resolving mediators (SPMs), derived from essential fatty acids, play an immunoregulatory role. Formyl peptide receptor-1 is a pattern recognition receptor that mediate host-defense and inflammation. On the other hand, FPR2 binds SPMs to induce resolution of inflammation. It is well known that low-grade chronic inflammation is present in hypertension, but it is unknown whether this phenomenon occurs due to dysregulation of resolution of inflammation. Also, it is unclear if arteries can sense SPM. We hypothesized that the resolution of inflammation is decreased in hypertension, and treatment with SPM will improve vascular function via FPR-2. Forty-five eicosanoids, precursors of SPMs were detected in the plasma of male Wistar Kyoto rats (WKY) (14 weeks old, n=10) and spontaneously hypertensive rats (SHR; 14 weeks old, n=16). Analysis revealed a significant decrease (%) in 5 different eicosanoids in SHR (1) free eicosapentaenoic acid (60%), (2) free adrenic acid (25%), (3) 20-carboxy-arachidonic acid (52%) (4) 5-hydroxyeicosatetraenoic acid (20%), and (5) 14,15-epoxyeicosa-5,8,11-trienoic acid (14,15-EET) (48%). Additionally, mesenteric resistance arteries (MRA, lumen diameter &lt; 300 μm) from SHR rats showed significant oxidative degradation of lipids measured by the presence of 4-hydroxynonenal (4-HNE) (4-HNE; AU: WKY: 3.8±0.6 vs. SHR: 14.4±3.8; p=0.02). MRA were mounted in a wire myograph to evaluate vascular function, and concentration-response curves (CRC) to acetylcholine (ACh 10−9 to 10−5 mol/L) were performed. As expected, relaxation was impaired in MRA from SHR compared to WKY. This was noted by a shift to the right in the CRC, increasing (%) area under the curve (ΔAUC: 20± 4%). On the other hand, SPMs (10 nM) restored this response by shifting the CRC to the left and reducing the AUC compared to arteries from SHR treated with vehicle [SPMs: Resolvin D1 (RvD1) (ΔAUC:19±4%), Resolvin E1 (RvE1) (ΔAUC: 8.5 ± 9%), and lipoxin A4 (ΔAUC: 20±7%,)]. Specific antagonism of FPR-2 (WRW4, 1μM) abolished the improvement in relaxation induced by SPMs. Superoxide indicator dihydroethidium (DHE) was used in primary MRA endothelial cell culture. SPMs reduced the formation of reactive oxygen species after an inflammatory stimulus [Control: 99±2.5%; TNFα: 272± 50%; RvD1: 109±25%; RvE1: 111±22%; LXA4: 101±10%, A.U.). However, WRW4 did not change these responses. Total FPR2 and lipoxygenase 5 (LOX-5) protein expression was similar in arteries from WKY and SHR. However, there was an increase in LOX-5 serine 523 phosphorylation in SHR, suggesting a compensatory mechanism to increase local LXA4. Overall, SPMs play an important role to maintain vascular heath, and their effects occur both dependent and independent of FPR2 activation. Improvement of resolution of inflammation maybe a new treatment for for hypertension. National Institutes of Health - R00GM118885, R01HL149762, R00HL151889, and RO1DK132948. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Metabolomic signatures associated with weight gain and psychosis spectrum diagnoses: A pilot study.

Psychosis spectrum disorders (PSDs), as well as other severe mental illnesses where psychotic features may be present, like bipolar disorder, are associated with intrinsic metabolic abnormalities. Antipsychotics (APs), the cornerstone of treatment for PSDs, incur additional metabolic adversities including weight gain. Currently, major gaps exist in understanding psychosis illness biomarkers, as well as risk factors and mechanisms for AP-induced weight gain. Metabolomic profiles may identify biomarkers and provide insight into the mechanistic underpinnings of PSDs and antipsychotic-induced weight gain. In this 12-week prospective naturalistic study, we compared serum metabolomic profiles of 25 cases within approximately 1 week of starting an AP to 6 healthy controls at baseline to examine biomarkers of intrinsic metabolic dysfunction in PSDs. In 17 of the case participants with baseline and week 12 samples, we then examined changes in metabolomic profiles over 12 weeks of AP treatment to identify metabolites that may associate with AP-induced weight gain. In the cohort with pre-post data (n = 17), we also compared baseline metabolomes of participants who gained ≥5% baseline body weight to those who gained <5% to identify potential biomarkers of antipsychotic-induced weight gain. Minimally AP-exposed cases were distinguished from controls by six fatty acids when compared at baseline, namely reduced levels of palmitoleic acid, lauric acid, and heneicosylic acid, as well as elevated levels of behenic acid, arachidonic acid, and myristoleic acid (FDR < 0.05). Baseline levels of the fatty acid adrenic acid was increased in 11 individuals who experienced a clinically significant body weight gain (≥5%) following 12 weeks of AP exposure as compared to those who did not (FDR = 0.0408). Fatty acids may represent illness biomarkers of PSDs and early predictors of AP-induced weight gain. The findings may hold important clinical implications for early identification of individuals who could benefit from prevention strategies to reduce future cardiometabolic risk, and may lead to novel, targeted treatments to counteract metabolic dysfunction in PSDs.

IGF2 May Enhance Placental Fatty Acid Metabolism by Regulating Expression of Fatty Acid Carriers in the Growth of Fetus and Placenta during Late Pregnancy in Pigs.

Fatty acids (FAs) are essential substances for the growth and development of the fetus and placenta. The growing fetus and placenta must obtain adequate FAs received from the maternal circulation and facilitated by various placental FA carriers, including FA transport proteins (FATPs), FA translocase (FAT/CD36), and cytoplasmic FA binding proteins (FABPs). Placental nutrition transport was regulated by imprinted genes H19 and insulin-like growth factor 2 (IGF2). Nevertheless, the relationship between the expression patterns of H19/IGF2 and placental fatty acid metabolism throughout pig pregnancy remains poorly studied and unclear. We investigated the placental fatty acid profile, expression patterns of FA carriers, and H19/IGF2 in the placentae on Days 40 (D40), 65 (D65), and 95 (D95) of pregnancy. The results showed that the width of the placental folds and the number of trophoblast cells of D65 placentae were significantly increased than those of D40 placentae. Several important long-chain FAs (LCFAs), including oleic acid, linoleic acid, arachidonatic acid, eicosapentaenoic acid, and docosatetraenoic acid, in the pig placenta showed dramatically increased levels throughout pregnancy. The pig placenta possessed higher expression levels of CD36, FATP4, and FABP5 compared with other FA carriers, and their expression levels had significantly upregulated 2.8-, 5.6-, and 12.0-fold from D40 to D95, respectively. The transcription level of IGF2 was dramatically upregulated and there were corresponding lower DNA methylation levels in the IGF2 DMR2 in D95 placentae relative to D65 placentae. Moreover, in vitro experimentation revealed that the overexpression of IGF2 resulted in a significant increase in fatty acid uptake and expression levels of CD36, FATP4, and FABP5 in PTr2 cells. In conclusion, our results indicate that CD36, FATP4, and FABP5 may be important regulators that enhance the transport of LCFAs in the pig placenta and that IGF2 may be involved in FA metabolism by affecting the FA carriers expression to support the growth of the fetus and placenta during late pregnancy in pigs.

Ability of a Polyphenol-Rich Nutraceutical to Reduce Central Nervous System Lipid Peroxidation by Analysis of Oxylipins in Urine: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Isoprostanes (IsoPs) are lipid peroxidation biomarkers that reveal the oxidative status of the organism without specifying which organs or tissues it occurs in. Similar compounds have recently been identified that can assess central nervous system (CNS) lipid peroxidation status, usually oxidated by reactive oxygen species. These compounds are the neuroprostanes (NeuroPs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the F2t-dihomo-isoprotanes derived from adrenic acid (AdA). The aim of the present investigation was to evaluate whether the long-term nutraceutical consumption of high polyphenolic contents (600 mg) from fruits (such as berries) and vegetables shows efficacy against CNS lipid peroxidation in urine biomarkers. A total of 92 subjects (47 females, 45 males, age 34 ± 11 years old, weight 73.10 ± 14.29 kg, height 1.72 ± 9 cm, body mass index (BMI) 24.40 ± 3.43 kg/m2) completed a randomized, cross-over, double-blind study after an intervention of two periods of 16 weeks consuming either extract (EXT) or placebo (PLA) separated by a 4-week washout period. The results showed significant reductions in three AdA-derived metabolites, namely, 17-epi-17-F2t-dihomo-IsoPs (Δ -1.65 ng/mL; p < 0.001), 17-F2t-dihomo-IsoPs (Δ -0.17 ng/mL; p < 0.015), and ent-7(RS)-7-F2t-dihomo-IsoPs (Δ -1.97 ng/mL; p < 0.001), and one DHA-derived metabolite, namely, 4-F4t-NeuroP (Δ -7.94 ng/mL; p < 0.001), after EXT consumption, which was not observed after PLA consumption. These data seem to show the effectiveness of the extract for preventing CNS lipid peroxidation, as determined by measurements of oxylipins in urine through Ultra-High-Performance Liquid Chromatography triple quadrupole tandem mass spectrometry (UHPLC-QqQ-ESI-MS/MS).

Very Long-Chain Fatty Acids Change the Ethanol Tolerance of Drosophila melanogaster Larvae

This research tested the hypothesis that long-chain saturated fatty acids increase the order of cell membranes of an organism and minimize the detrimental fluidizing effects of ethanol. Unsaturated fatty acids increase membrane fluidity and are unlikely to increase the ethanol tolerance of the organism. Both a fatty acid-free medium and media supplemented with very long-chain fatty acids (20 or more carbons) were fed to wild-type larvae of Drosophila melanogaster; larvae were then transferred to media with or without ethanol to test for effects of the fatty acids on ethanol tolerance. Ethanol decreased the percent of larvae to pupate, and lengthened larval development time. However, the percentage of pupae to reach the adult stage and the weight of adult males increased when the larvae were fed ethanol. The very long-chain, unsaturated fatty acids, arachidonic acid [20:4(n-6)] and docosatetraenoic acid [22:4(n-6)], were associated with increased larval mortality when administered in a medium supplemented with ethanol. Arachidic acid (20:0) increased the percentage of larvae to pupate under ethanol stress, decreased the development time and increased the adult weight in the presence and absence of ethanol. Behenic acid (22:0) was not effectively incorporated into phospholipids and had little effect on growth traits. Thus, the experimental results were consistent with the hypothesis.

Effects of low-temperature stress on intestinal structure, enzyme activities and metabolomic analysis of juvenile golden pompano (Trachinotus ovatus)

Water temperature plays a crucial role in the growth, survival, and reproduction of fish species, as they make up the majority of aquatic fauna. In this study, the effects of low temperature were studied on the functional state of juvenile golden pompano (Trachinotus ovatus) under low-temperature stress. The study was conducted at 28°C in the control group and 18°C in the cold group for 14 d to determine the intestinal tissue, digestive and antioxidant enzyme activities, and metabolites of juvenile fish. The results showed that: (1) the swelling degree of the muscle layer deepened and was congested with a longer low-temperature stress period. The folds were sparse, from slight swelling to shedding and deformation. The intestinal mucosa was necrotic and had vacuoles, and the number gradually increased. Serious erosion of the villi occurred. (2) The specific activities of digestive enzymes showed a downward trend. (3) The intestinal superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and glutathione peroxidase (GSH-Px) activity showed an upward trend. The intestinal catalase (CAT) activity showed a downward trend. (4) Compared with the control group, there were 28 metabolites in the cold group showing significant differences, among which Z, 11Z, 14Z-eicosatrienoic acid, stearic acid, and adrenic acid showed an upward trend. In contrast, spermidine and uracil showed a downward trend. Among the enriched metabolic pathways, the main differential pathways were unsaturated fatty acid biosynthesis, fatty acid biosynthesis, linoleic acid metabolism, pyrimidine metabolism, and β-alanine metabolism. According to metabolomic analysis, under low-temperature stress, the fish body improved the synthesis of unsaturated fatty acids and saturated fatty acids to adapt to a low-temperature environment and consumed spermidine to improve its immune ability to clear the peroxide generated by the synthesis of unsaturated fatty acids in the body so that the cells were protected from oxidative damage. After 14 days, low-temperature stress affected metabolites and enzyme activity indices in juvenile golden pompano. Low-temperature stress causes changes in intestinal antioxidants and digestive enzymes and damage intestinal tissues. As a result of this exploration of how low temperatures affect the juvenile golden pompano, the foundation is laid for future studies, such as the molecular mechanisms of low-temperature adaptation in fish species.

7,10,13,16-Docosatetraenoic acid impairs neurobehavioral development by increasing reactive oxidative species production in Caenorhabditis elegans

AimsTo investigate human breast milk (HBM) lipids that may adversely affect infant neurodevelopment. Main methodsWe performed multivariate analyses that combined lipidomics and psychologic Bayley-III scales to identify which HBM lipids are involved in regulating infant neurodevelopment. We observed a significant moderate negative correlation between 7,10,13,16-docosatetraenoic acid (omega-6, C22H36O2, the common name adrenic acid, AdA) and adaptive behavioral development. We further studied the effects of AdA on neurodevelopment by using Caenorhabditis elegans (C. elegans) as a model. Worms from larval stages L1 to L4 were supplemented with AdA at 5 nominal concentrations (0 μM [control], 0.1 μM, 1 μM, 10 μM, and 100 μM) and subjected to behavioral and mechanistic analyses. Key findingsSupplementation with AdA from larval stages L1 to L4 impaired neurobehavioral development, such as locomotive behaviors, foraging ability, chemotaxis behavior, and aggregation behavior. Furthermore, AdA upregulated the production of intracellular reactive oxygen species. AdA-induced oxidative stress blocked serotonin synthesis and serotoninergic neuron activity and inhibited expression of daf-16 and the daf-16–regulated genes mtl-1, mtl-2, sod-1, and sod-3, resulting in attenuation of the lifespan in C. elegans. SignificanceOur study reveals that AdA is a harmful HBM lipid that may have adverse effects on infant adaptive behavioral development. We believe this information may be critical for AdA administration guidance in children's health care.

Comparison of the gut microbiota and metabolites between Diannan small ear pigs and Diqing Tibetan pigs.

Host genetics and environment participate in the shaping of gut microbiota. Diannan small ear pigs and Diqing Tibetan pigs are excellent native pig breeds in China and live in different environments. However, the gut microbiota of Diannan small ear pigs and Diqing Tibetan pigs were still rarely understood. Therefore, this study aimed to analyze the composition characteristics of gut microbiota and metabolites in Diannan small ear pigs and Diqing Tibetan pigs. Fresh feces of 6 pigs were randomly collected from 20 4-month-old Diannan small ear pigs (DA group) and 20 4-month-old Diqing Tibetan pigs (TA group) for high-throughput 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS) non-targeted metabolome analysis. The results revealed that Firmicutes and Bacteroidetes were the dominant phyla in the two groups. Chao1 and ACE indices differed substantially between DA and TA groups. Compared with the DA group, the relative abundance of Prevotellaceae, and Ruminococcus was significantly enriched in the TA group, while the relative abundance of Lachnospiraceae, Actinomyces, and Butyricicoccus was significantly reduced. Cholecalciferol, 5-dehydroepisterol, stigmasterol, adrenic acid, and docosahexaenoic acid were significantly enriched in DA group, which was involved in the steroid biosynthesis and biosynthesis of unsaturated fatty acids. 3-phenylpropanoic acid, L-tyrosine, phedrine, rhizoctin B, and rhizoctin D were significantly enriched in TA group, which was involved in the phenylalanine metabolism and phosphonate and phosphinate metabolism. We found that significant differences in gut microbiota composition and metabolite between Diannan small ear pigs and Diqing Tibetan pigs, which provide a theoretical basis for exploring the relationship between gut microbiota and pig breeds.

F4-neuroprostanes and F2-dihomo-isoprostanes: biomarkers and bioactive oxylipins

Under condition of oxidative stress, free radical-catalyzed peroxidation of docosahexaenoic acid (DHA) and adrenic acid (AdA) generates in vivo neuroprostanes (NeuroPs) and dihomo-isoprostanes (dihomo-IsoPs), among a large number of key products participating in many pathophysiological processes. These non-enzymatic oxygenated metabolites display a wide range of biological actions (especially DHA-metabolites), and some of them are now considered as the most reliable indicators of oxidative stress in neurogenerative, neurodevelopmental or cardiovascular diseases. In this review, we will present an overview regarding neuroprostanes and dihomo-isoprostanes and discuss about their biological interests.

Causal effects of fatty acids on depression: Mendelian randomization study.

Fatty acids (FA) are widely believed to play a role in the pathophysiology of depression. However, the causal relationships between FA and depression remain elusive and warrant further research. We aimed to investigate the potential causal relationship between FA [saturated fatty acids (SFA), mono-unsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA)] and the risk of depression using Mendelian randomization (MR) analysis. We conducted a two-sample MR analysis using large-scale European-based genome-wide association studies (GWASs) summary data related to depression (n = 500,199 individuals) and FA [saturated fatty acids (SFA), mono-unsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA)] levels. MR analysis was performed using the Wald ratio and inverse variance-weighted (IVW) methods, and sensitivity analysis was conducted by the simple mode, weighted mode, weighted median method, and MR-Egger method. We found the causal effects for the levels of oleic acid (OA; OR = 1.07, p = 5.72 × 10-4), adrenic acid (OR = 0.74, p = 1.01 × 10-3), α-linolenic acid (ALA; OR = 2.52, p = 1.01 × 10-3), eicosapentaenoic acid (EPA; OR = 0.84, p = 3.11 × 10-3) on depression risk, after Bonferroni correction. The sensitivity analyses indicated similar trends. No causal effect between the levels of SFA and depression risk was observed. Our study suggests that adrenic acid and EPA are protective against the risk of depression, while OA and ALA are potential risk factors for depression. Nonetheless, the underlying mechanisms that mediate the association between these FAs and depression risk should be investigated in further experiments.

Age-associated changes in circulatory fatty acids: new insights on adults and long-lived individuals.

Long-lived individuals (LLIs) are considered an ideal model to study healthy human aging. Blood fatty acid (FA) profile of a cohort of LLIs (90-111years old, n = 49) from Sicily was compared to adults (18-64years old, n = 69) and older adults (65-89years old, n = 54) from the same area. Genetic variants in key enzymes related to FA biosynthesis and metabolism were also genotyped to investigate a potential genetic predisposition in determining the FA profile. Gas chromatography was employed to determine the FA profile, and genotyping was performed using high-resolution melt (HRM) analysis. Blood levels of total polyunsaturated FA (PUFA) and total trans-FA decreased with age, while the levels of saturated FA (SFA) remained unchanged. Interestingly, distinctively higher circulatory levels of monounsaturated FA (MUFA) in LLIs compared to adults and older adults were observed. In addition, among LLIs, rs174537 in the FA desaturase 1/2 (FADS1/2) gene was associated with linoleic acid (LA, 18:2n-6) and docosatetraenoic acid (DTA, 22:4n-6) levels, and the rs953413 in the elongase of very long FA 2 (ELOVL2) was associated with DTA levels. We further observed that rs174579 and rs174626 genotypes in FADS1/2 significantly affect delta-6 desaturase (D6D) activity. In conclusion, our results suggest that the LLIs have a different FA profile characterized by high MUFA content, which indicates reduced peroxidation while maintaining membrane fluidity.

Changes in fatty acid levels after consumption of a novel docosahexaenoic supplement from algae: a crossover randomized controlled trial in omnivorous, lacto-ovo vegetarians and vegans

PurposeTo determine serum fatty acids of lacto-ovo vegetarian (LOV), vegan (VEG) and omnivorous (OMN) adults, and to analyse the effects of consuming a docosahexaenoic acid (DHA) supplement of vegetable origin on fatty acid profile.MethodsA randomized, double-blind, placebo-controlled crossover design was conducted in healthy adults. Volunteers (n = 116) were randomly assigned to a DHA-supplement (dose 250 mg/day), made from the microalgae Schizochytrium sp., or a placebo during 5-week periods separated by a 5-week washout interim period. Compliance and dietary intake were estimated and serum fatty acids were determined by gas chromatography. Results were analysed by mixed linear models.ResultsPercentage of linoleic acid (C18:2n6) in serum was the highest among the fatty acids in the three diet groups, followed by oleic (C18:1n9) and palmitic (C16:0) acids. Linoleic (C18:2n6) and alpha-linolenic (C18:3n3) acids were higher in VEG compared to OMN (p < 0.001), while in LOV, their levels were intermediate between the other groups. Women presented higher DHA (C22:6n3) than men (p < 0.001). The DHA-supplement increased serum DHA compared to placebo in the three diet groups (p < 0.001), and a higher increase was observed in VEG followed by LOV (p < 0.001). The ratio serum n-6/n-3 improved by the supplementation but remained higher in LOV and VEG than in OMN. In contrast, the DHA-supplement decreased docosapentaenoic (C22:5n3) and docosatetraenoic (C22:4n6) acids in all diet groups (p < 0.001) and increased the eicosapentaenoic to alpha-linolenic fatty acids ratio (p = 0.016).ConclusionThe DHA-supplement at dose of 250 mg/day was effective in increasing serum DHA either in omnivorous, lacto-ovo vegetarian and vegan adults.Clinical trial registrationRegistered at Clinicaltrials.gov (www.clinicaltrials.gov), NCT04278482.

Identification of biomarkers associated with the feed efficiency by metabolomics profiling: results from the broiler lines divergent for high or low abdominal fat content

BackgroundImproving feed efficiency (FE) is one of the main objectives in broiler breeding. It is difficult to directly measure FE traits, and breeders hence have been trying to identify biomarkers for the indirect selection and improvement of FE traits. Metabolome is the "bridge" between genome and phenome. The metabolites may potentially account for more of the phenotypic variation and can suitably serve as biomarkers for selecting FE traits. This study aimed to identify plasma metabolite markers for selecting high-FE broilers. A total of 441 birds from Northeast Agricultural University broiler lines divergently selected for abdominal fat content were used to analyze plasma metabolome and estimate the genetic parameters of differentially expressed metabolites.ResultsThe results identified 124 differentially expressed plasma metabolites (P < 0.05) between the lean line (high-FE birds) and the fat line (low-FE birds). Among these differentially expressed plasma metabolites, 44 were found to have higher positive or negative genetic correlations with FE traits (|rg| ≥ 0.30). Of these 44 metabolites, 14 were found to display moderate to high heritability estimates (h2 ≥ 0.20). However, among the 14 metabolites, 4 metabolites whose physiological functions have not been reported were excluded. Ultimately, 10 metabolites were suggested to serve as the potential biomarkers for breeding the high-FE broilers. Based on the physiological functions of these metabolites, reducing inflammatory and improving immunity were proposed to improve FE and increase production efficiency.ConclusionsAccording to the pipeline for the selection of the metabolite markers established in this study, it was suggested that 10 metabolites including 7-ketocholesterol, dimethyl sulfone, epsilon-(gamma-glutamyl)-lysine, gamma-glutamyltyrosine, 2-oxoadipic acid, L-homoarginine, testosterone, adenosine 5'-monophosphate, adrenic acid, and calcitriol could be used as the potential biomarkers for breeding the "food-saving broilers".

Alterations in bone metabolites with age in C57BL/6 mice model.

Understanding the pathophysiology behind age-related diseases is an urgent need as the elderly population continues to grow. With age, there is a high risk of musculoskeletal deterioration and associated morbidity and mortality. Although the exact mechanism behind age-related degeneration is unknown, it is well established that alteration in cellular metabolism is one of the important contributing factors. Alteration in signaling pathways with age leads to the accumulation or depletion of several metabolites that play a vital role in musculoskeletal pathophysiology. This study aimed to identify age-related changes in bone tissue metabolites in C57BL/6 mice. We then correlated the differentially expressed metabolites with their functions in bone biology. In both aged males and females, hydroxyproline, glutamine, and alpha-linolenic acid levels were decreased. In aged females, Ornithine (p value = 0.001), L-Proline (p value = 0.008), Uridine (p value = 0.001), Aspartic Acid (p value = 0.004) levels were significantly decreased, and glutamate (p value = 0.002) was elevated. In aged males, N-acetyl-D-glucosamine (pvalue = 0.010), Adrenic acid (pvalue = 0.0099), Arachidonic acid (p value = 0.029) and Allantoin (p value = 0.004) levels were decreased. Metabolic pathway analysis revealed that purine and D-glutamine and D-glutamate metabolism were significantly altered in both sexes, while arginine biosynthesis in females and lipid metabolism in males were highly affected. These differences in metabolic signaling might be one of the reasons for the discrepancy in musculoskeletal disease manifestation between the two sexes. Understanding the role of these metabolites play in the aging bone will allow for new sex-specific targeted therapies against the progression of musculoskeletal diseases.

Plasma polyunsaturated fatty acid concentrations and sleep apnea risk: A two-sample Mendelian randomization study.

BackgroundPrevious observational studies have found that lower levels of circulating polyunsaturated fatty acids (PUFAs) were associated with a higher risk of sleep apnea (SA). However, the causality of the association remains unclear.Materials and methodsWe used the two-sample Mendelian randomization (MR) study to assess the causal association of omega-3 and omega-6 fatty acids with SA. Single-nucleotide polymorphisms (SNPs) predicting the plasma level of PUFAs at the suggestive genome-wide significance level (p < 5 × 10–6) were selected as instrumental variables (IVs) from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) (n = ∼8,000) Consortium. For outcomes, the summary-level statistics of SA were obtained from the latest genome-wide association study (GWAS), which combined five cohorts with a total number of 25,008 SA cases and 172,050 snoring cases (total = 523,366).ResultsWe found no association of α-linolenic acid (ALA) [odds ratio (OR) = 1.09 per% changed, 95% confidence interval (CI) 0.67–1.78], eicosapentaenoic acid (EPA) (OR = 0.94, 95% CI 0.88–1.01), docosapentaenoic acid (DPA) (OR = 0.95, 95% CI 0.88–1.02), and docosahexaenoic acid (DHA) (OR = 0.99, 95% CI 0.96–1.02) with the risk of SA using inverse-variance weighted (IVW) method. Moreover, for omega-6 PUFAs, no association between linoleic acid (LA) (OR = 0.98, 95% CI 0.96–1.01), arachidonic acid (AA) (1.00, 95% CI 0.99–1.01), and adrenic acid (AdrA) (0.93, 95% CI 0.71–1.21) with the risk of SA was found. Similarly, no associations of PUFAs with SA were found in single-locus MR analysis.ConclusionIn the current study, we first found that there is no genetic evidence to support the causal role of omega-3 and omega-6 PUFAs in the risk of SA. From a public health perspective, our findings refute the notion that consumption of foods rich in PUFAs or the use of PUFAs supplementation can reduce the risk of SA.

Plasma phospholipid polyunsaturated fatty acids composition in early pregnancy and fetal growth trajectories throughout pregnancy: Findings from the US fetal growth studies-singletons cohort.

SummaryBackgroundWe aimed to investigate plasma phospholipid PUFA levels in early pregnancy and fetal growth trajectories throughout pregnancy.MethodsWithin the NICHD Fetal Growth Studies–Singleton Cohort, we enrolled 2,802 pregnant women at gestational weeks 8–13 and randomly assigned them to four ultrasonogram schedules to capture weekly fetal growth throughout pregnancy. Eleven plasma phospholipid PUFAs were measured at early pregnancy using blood samples collected from a subsample of 321 pregnant women. We modeled fetal growth trajectories across tertiles of PUFAs with cubic splines using linear mixed models after adjusting for major confounders. We then compared pairwise weekly fetal growth biometrics referencing the lowest tertile in each PUFA using the Wald test.FindingsAmong plasma n-3 PUFAs in early pregnancy, docosahexaenoic acid (DHA, 22:6n3) and alpha-linolenic acid (ALA, 18:3n3) showed positive associations with all fetal growth measurements. For instance, compared with the lowest tertile, the highest tertile of DHA had greater estimated fetal growth (EFW) and abdominal circumference (AC), starting at 13 weeks of gestation and throughout pregnancy (at gestational week 38: 3235.3 vs. 3089.0 g for EFW; 344.6 vs. 339.2 mm for AC). As for plasma n-6 PUFAs, some showed positive associations (e.g., linoleic acid [LA], 18:2n6) while others (e.g., docosatetraenoic acid [DTA], 22:4n6) showed inverse associations with fetal growth measures.InterpretationOur data suggested that higher plasma levels of DHA and ALA in the first trimester were associated with increased fetal size and weight throughout subsequent pregnancy.FundingNational Institute of Child Health and Human Development intramural funding.

MCD Diet Rat Model Induces Alterations in Zinc and Iron during NAFLD Progression from Steatosis to Steatohepatitis.

We evaluate the effects of the methionine-choline-deficient (MCD) diet on serum and hepatic zinc (Zn) and iron (Fe) and their relationships with matrix metalloproteinases (MMPs) and their modulators (TIMPs and RECK) as well as hepatic fatty acids using male Wistar rats fed 2-, 4- and 8-week MCD diets. Serum and hepatic Zn decrease after an 8-week MCD diet. Serum Fe increases after an 8-week MCD diet and the same occurs for hepatic Fe. An increase in hepatic MMP activity, associated with a decrease in RECK and TIMPs, is found in the MCD 8-week group. Liver Fe shows a positive correlation versus MMPs and RECK, and an inverse correlation versus TIMPs. A positive correlation is found comparing liver Zn with stearic, vaccenic and arachidonic acids, and an inverse correlation is found with linolenic and docosatetraenoic acids. An opposite trend is found between liver Fe versus these fatty acids. During NAFLD progression from steatosis to steatohepatitis, MCD rats exhibit an increase in Zn and a decrease in Fe levels both in serum and tissue associated with alterations in hepatic MMPs and their inhibitors, and fatty acids. The correlations detected between Zn and Fe versus extracellular matrix modulators and fatty acids support their potential role as therapeutic targets.

Changes in Phospholipid Composition of the Human Cerebellum and Motor Cortex during Normal Ageing.

(1) Background: Changes in phospholipid (phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine, i.e., PC, PE and PS) composition with age in the mitochondrial and microsomal membranes of the human cerebellum and motor cortex were examined and compared to previous analyses of the prefrontal cortex, hippocampus and entorhinal cortex. (2) Methods: Nano-electrospray ionization on a hybrid triple quadrupole–linear ion trap mass spectrometer was used to analyse the brain regions of subjects aged 18–104 years. (3) Results: With age, the cerebellum showed many changes in the major phospholipids (>10% of the phospholipid class). In both membrane types, these included increases in PE 18:0_22:6 and PS 18:0_22:6, decreases in PE 18:0_20:4 and PS 18:0_18:1 and an increase in PC 16:0_16:0 (microsomal membrane only). In addition, twenty-one minor phospholipids also changed. In the motor cortex, only ten minor phospholipids changed with age. With age, the acyl composition of the membranes in the cerebellum increased in docosahexaenoic acid (22:6) and decreased in the arachidonic (20:4) and adrenic (22:4) acids. A comparison of phospholipid changes in the cerebellum, motor cortex and other brain areas is provided. (4) Conclusions: The cerebellum is exceptional in the large number of major phospholipids that undergo changes (with consequential changes in acyl composition) with age, whereas the motor cortex is highly resistant to change.