Plasma Fatty Acid Research Articles

The sports performance improving effects of konjac glucomannan with varying molecular weights in overtrained mice

Overtraining affects individuals engaged in high-volume training, potentially hindering athletic performance and revealing shortcomings in suggested solutions. This study evaluated the impact of konjac glucomannan (KGM) with varying molecular weights on the gut microbiome, endurance, and strength in mice subjected to excessive training. The native KGM (1.82 × 107 Da) was enzymatically degraded using endo-1,4-β-mannanase to generate moderate molecular weight KGM (KGM-EM, 1.89 × 105 Da) and low molecular weight KGM (KGM-EL, 1.34 × 104 Da). These fractions were characterized and compared with the native KGM regarding their effects on mice undergoing excessive training. The results demonstrated a positive correlation between KGM's molecular weight and its capacity to mitigate the adverse impacts of excessive training on strength or/and endurance (a significant increase of 55.57 % and 55.70 % by the native KGM compared with the excessive training group). In addition, the native KGM exhibited superior preservation of microbial diversity and composition in fecal samples against excessive training-induced shifts, along with increased production of individual and total short-chain fatty acids in plasma compared with the two degraded products. Overall, these results highlight the potential benefits of high molecular weight KGM for preventing overtraining syndrome and enhancing athletic performance in animal models.

Effects of Different Technological Forms of the Perilla frutescens in the Diet on Ruminal Fermentation, Milk and Plasma Fatty Acid Composition, Ruminal Biohydrogenation and Milk Quality in Dairy Goats.

Fatty acids can be protected by changing their structure or form against microbial activity, and the different forms of fatty acids can modulate the ruminal biohydrogenation rate and contribute to the desired fatty acid profile in milk fat. The study investigated the effects of perilla (Perilla frutescens) dietary supplementation in the diet in different technological forms (seed, oil and formaldehyde-treated oil) on milk, plasma and ruminal fatty acid composition, and milk quality in lactating goats. The four dietary treatments consisted of (1) no supplementation, basal diet (CON); (2) perilla supplementation as seed at 44.7g/kg (consisting of 20g/kg oil (PS)); (3) perilla supplementation as oil at 20g/kg (PO); (4) perilla supplementation as formaldehyde treated oil at 20g/kg (protected perilla oil [PPO]). The experiment was implemented in a double 4×4 Latin square trial design, and sampling was carried out for 7 days after 21 days of adaptation. Performance parameters were not affected by P. frutescens supplementation to the diet. PO decreased milk fat, whereas PPO increased milk fat. Milk cholesterol was not affected by P. frutescens dietary supplementation. Perilla oil supplementation in different forms to the diet did not affect ruminal pH, VFA and methane production. Perilla oil supplementation in different forms to the diet did not also affect the concentration of blood serum glucose, cholesterol and non-esterified fatty acids. Perilla supplementation to the diet increased the milk conjugated linoleic acid (CLA), C18:3n-3, C22:5n-3, C20:5n-3, C22:6n-3 and polyunsaturated fatty acid (PUFA) concentrations, and PPO group showed the greatest values. Ruminal palmitic (C16:0) acid was decreased, and in perilla groups, stearic acid (C18:0) concentration had the lowest, and ruminal c-9, t-11 CLA concentration had the highest value in PPO. It has been found that the most effective form of perilla oil in increasing milk quality is that with formaldehyde treatment (protected form). Perilla oil, which is a rich source of omega 3 in the diet, can be used to increase milk quality in goats without adversely affecting performance, ruminal fermentation and blood parameters.

Circulating fatty acids, genetic susceptibility and hypertension: a prospective cohort study.

Combining genetic risk factors and plasma fatty acids (FAs) can be used as an effective method of precision medicine to prevent hypertension risk. A total of 195,250 participants in the UK Biobank cohort were included in this study from 2006-2010. Polygenic risk scores (PRSs) were calculated for hypertension using single-nucleotide polymorphisms (SNPs). Concentrations of plasma FAs, including polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs) and saturated fatty acids (SFAs), were tested by nuclear magnetic resonance. The Cox model was used to test for the main effects of PRS, different plasma FAs and their joint effects on hypertension. Relative excess risk due to interaction (RERI) and the attributable proportion due to interaction (AP) were used to test the additive interaction. Plasma PUFAs, n-3 PUFAs, MUFAs and SFAs were related to the risk of hypertension (PUFAs: HR, 0.878; 95% CI, 0.868-0.888; MUFAs: HR, 1.13; 95% CI, 1.123-1.150; SFAs: HR, 1.086; 95% CI, 1.074-1.098; n-3 PUFAs: HR, 0.984; 95% CI, 0.973-0.995). Moreover, an additive interaction was found between PRS and plasma FAs, which could contribute to an approximately 10-18% risk of hypertension, and the associations between high plasma MUFAs and a high PRS of hypertension were the strongest positive [RERI: 0.178 (95% CI: 0.062, 0.294), AP: 0.079 (95% CI: 0.027, 0.130)]. Increased plasma MUFAs or SFAs and decreased plasma PUFAs or n-3 PUFAs were associated with hypertension risk, especially among people at high genetic risk.

Bidirectional Mendelian Randomization Analysis of Genetic Proxies of Plasma Fatty Acids and Pre-Eclampsia Risk.

Previous studies have reported associations between fatty acids and the risk of pre-eclampsia. However, the causality of these associations remains uncertain. This study postulates a causal relationship between specific plasma fatty acids and pre-eclampsia or other maternal hypertensive disorders (PE-HTPs). To test this hypothesis, two-sample bidirectional Mendelian randomization (MR) analyses were employed to determine the causality effects. Single-nucleotide polymorphisms associated with PE-HTPs and fatty acids were obtained from a genome-wide association study (GWAS) of European ancestry. Bidirectional MR analyses were conducted using methods such as inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses, including tests for heterogeneity, horizontal pleiotropy, and co-localization, were conducted to assess the robustness of MR results. The analyses revealed causal relationships between PE-HTPs and several fatty acids, including monounsaturated fatty acid (MUFA), omega-6 fatty acid (n-6 FA), linoleic acid (LA), docosahexaenoic acid (DHA), and the PUFA/MUFA ratio. Genetically predicted higher risk of PE-HTPs was significantly associated with lower plasma n-6 FA (OR = 0.96, 95% CI: 0.93-0.99), particularly LA (OR = 0.95, 95% CI: 0.92-0.98). Conversely, increased DHA (OR = 0.86, 95% CI: 0.78-0.96) and a higher PUFA/MUFA ratio (OR = 0.86, 95% CI: 0.76-0.98) were associated with a reduced risk of PE-HTPs. Elevated MUFA levels (OR = 1.12, 95% CI: 1.00-1.25) were related to an increased risk. This study provides robust genetic evidence supporting bidirectional causal relationships between PE-HTPs and specific plasma fatty acids, underscoring the critical role of fatty acid metabolism in maternal hypertensive disorders.

Thrombolysis exacerbates cerebrovascular injury after ischemic stroke via a VEGF-B dependent effect on adipose lipolysis.

Cerebrovascular injuries leading to edema and hemorrhage after ischemic stroke are common. The mechanisms underlying these events and how they are connected to known risk factors for poor outcome, like obesity and diabetes, is relatively unknown. Herein we demonstrate that increased adipose tissue lipolysis is a dominating risk factor for the development of a compromised cerebrovasculature in ischemic stroke. Reducing adipose lipolysis by VEGF-B antagonism improved vascular integrity by reducing ectopic cerebrovascular lipid deposition. Thrombolytic therapy in ischemic stroke using tissue plasminogen activator (tPA) leads to increased risk of hemorrhagic complications, substantially limiting the use of thrombolytic therapy. We provide evidence that thrombolysis with tPA promotes adipose tissue lipolysis, leading to a rise in plasma fatty acids and lipid accumulation in the ischemic cerebrovasculature after stroke. VEGF-B blockade improved the efficacy and safety of thrombolysis suggesting the potential use of anti-VEGF-B therapy to extend the therapeutic window for stroke management.

Fatty acids from nutrition sources for preterm infants and their effect on plasma fatty acid profiles

BackgroundIn preterm infants, IV administration of fat is less well tolerated compared to intake via the enteral route, often resulting in hypertriglyceridemia. It is therefore recommended that parenteral fat intake should not exceed 3.5 to 4.0 g/kg/d whereas human milk can provide up to 8 g/kg/d. It is unknown whether such hypertriglyceridemic conditions are caused by a uniform increase of all fatty acids or it is linked to an elevation of distinct fatty acids due to an unbalanced intake. Obviously, both scenarios could potentially influence the formulation of novel lipid solutions for preterm infants. Objective of this exploratory study was to compare fatty acid profiles between a) different nutritional sources and corresponding plasma samples, b) plasma of infants fed breast milk versus those receiving lipid emulsion, and c) plasma of infants with normal versus elevated triglyceride levels.MethodsForty-seven preterm infants < 36 weeks of gestation were included; fatty acid profiles were measured in serum samples and corresponding nutritional sources (breast milk and lipid emulsion) using gas chromatography/mass spectrometry.ResultsCompared to breast milk levels, plasma contained significantly lower C8:0, C10:0, C12:0, C14:0, C19:1n9, C18:3n3 (p < 0.0001). In contrast, relative abundance of C16:0, C18:0 and C20:4n6 was higher in plasma than in corresponding breast milk samples (p < 0.001) and lipid emulsion (p < 0.01). Compared to the corresponding lipid emulsion, the abundance of C18:2n6 and C18:3n3 was significantly lower in plasma (p < 0.001). Fatty acid profiles in plasma of infants fed breast milk compared to lipid emulsion were not markedly different. Hypertriglyceridemic samples showed elevated levels for C18:1n9 and C16:0 when compared with normotriglyceridemic samples.ConclusionsOur study reveals that lipid levels in plasma show both depletion and enrichment of distinct fatty acids which do not seem to be closely related to dietary intake. A more detailed understanding of fatty acid flux rates is needed, like the understanding of amino acid metabolism and is supported by the finding that hypertriglyceridemia might be a state of selective fatty acid accumulation. This would allow to develop more balanced diets for intensive care and potentially improve clinical outcomes.

Metabolomic analysis reveals the potential of fucosylated chondroitin sulfate from sea cucumber in modulating metabolic homeostasis

In this study, we prepared four derivatives of fucosylated chondroitin sulfate (FCS): full-length FCS (flFCS) from Holothuria leucospilota, low molecular weight FCS (lmFCS) derived from flFCS, and their de-branched counterparts, de-branched flFCS (d-flFCS) and de-branched lmFCS (d-lmFCS) via controlled acid treatment. Following structural verification using various analytical techniques, we applied targeted metabolomics to examine the impact of FCS on nutritional efficacy and its structure-activity relationship. Analysis of 225 plasma and feces samples from 75 mice revealed a positive correlation between metabolomic shifts and increased weight gain, underscoring FCS’s potential to enhance nutrient absorption and promote growth. The observed linear relationship between the levels of short-chain fatty acids in plasma and feces suggests that FCS may facilitate catabolic activities in the gastrointestinal tract. The comparative study of different FCS derivatives on mouse growth and metabolic homeostasis regulation led to the conclusion that FCS exhibits greater biological activity with a higher degree of branching and larger molecular weight.

Adherence to the Healthy Nordic Food Index is associated with reduced plasma levels of inflammatory markers in patients with heterozygous familial hypercholesterolemia

Background and aimsFamilial hypercholesterolemia (FH) is an inherited disease associated with hypercholesterolemia, and dietary treatment is part of the treatment. We aimed to assess the dietary pattern in relation to the Healthy Nordic Food Index (HNFI) in adults with and without heterozygous FH (HeFH), and to examine the associations between dietary quality and biomarkers related to cardiovascular disease in adults with HeFH. MethodsWe included 205 adults (≥18 years) with HeFH who received follow-up at the Lipid Clinic in Oslo and compared them to controls (n=228). Dietary intake was assessed using a food frequency questionnaire and dietary quality was assessed using the HNFI. Blood samples were analysed for levels of blood lipids, plasma fatty acids (FAs), and markers of inflammation and platelet activation. ResultsThe HeFH patients (median 60 years; 50.2% female; 25.9% in secondary prevention) had lower intake of total and saturated fat compared to controls (32.6 energy percent (E%) vs. 34.9E%, and 9.6 E% vs 12.0 E%, respectively; p<0.001 for both). In the HeFH patients, increasing dietary quality was associated with increased plasma levels of the n-3 polyunsaturated FAs (PUFAs) eicosapentaenoic acid and docosahexaenoic acid, and the n-6 PUFA linoleic acid, and lower plasma levels of the inflammatory cytokines Tumor Necrosis Factor and interleukin-6, and of the platelet-derived inflammatory cytokines Platelet Factor 4 and Neutrophil-Activating Peptide-2. ConclusionNorwegian patients with HeFH followed up at a Lipid Clinic eat healthier than controls. Adherence to a healthy dietary pattern is associated with higher plasma levels of n-3 and n-6 PUFA, and lower levels of inflammatory markers, including platelet markers. This may suggest that adherence to an overall healthy dietary pattern might be beneficial for HeFH patients independent of the cholesterol-lowering effect of the diet.

Markers of Metabolic Abnormalities in Vitiligo Patients.

While vitiligo is primarily caused by melanocyte deficiency or dysfunction, recent studies have revealed a notable prevalence of metabolic syndrome (MetS) among patients with vitiligo. This suggests shared pathogenic features between the two conditions. Individuals with vitiligo often exhibit variations in triglyceride levels, cholesterol, and blood pressure, which are also affected in MetS. Given the similarities in their underlying mechanisms, genetic factors, pro-inflammatory signalling pathways, and increased oxidative stress, this study aims to highlight the common traits between vitiligo and metabolic systemic disorders. Serum analyses confirmed increased low-density lipoprotein (LDL) levels in patients with vitiligo, compared to physiological values. In addition, we reported significant decreases in folate and vitamin D (Vit D) levels. Oxidative stress is one of the underlying causes of the development of metabolic syndromes and is related to the advancement of skin diseases. This study found high levels of inflammatory cytokines, such as interleukin-6 (IL-6) and chemokine 10 (CXCL10), which are markers of inflammation and disease progression. The accumulation of insulin growth factor binding proteins 5 (IGFBP5) and advanced glycation end products (AGEs) entailed in atherosclerosis and diabetes onset, respectively, were also disclosed in vitiligo. In addition, the blood-associated activity of the antioxidant enzymes catalase (Cat) and superoxide dismutase (SOD) was impaired. Moreover, the plasma fatty acid (FAs) profile analysis showed an alteration in composition and specific estimated activities of FAs biosynthetic enzymes resembling MetS development, resulting in an imbalance towards pro-inflammatory n6-series FAs. These results revealed a systemic metabolic alteration in vitiligo patients that could be considered a new target for developing a more effective therapeutic approach.

Plasma levels of EPA and DHA after ingestion of a single dose of EPA and DHA ethyl esters

AbstractOmega‐3 polyunsaturated fatty acids (n3 PUFA), specifically eicosapentaenoic acid (EPA, 20:5n3), and docosahexaenoic acid (DHA, 22:6n3), are essential for maintaining health. To better understand their biology, it is important to define their bioavailability. The aim of this cross‐over study was to investigate and compare the acute effects on plasma EPA and DHA levels after single doses of EPA oil (99% pure) and DHA (97% pure) ethyl esters. Twelve men aged 20–40 years with a body‐mass‐index of 20–27 kg/m2 and low fish consumption were recruited. Several measures (e.g., 4‐week run‐in period, standardized diet, and blood collection protocols) were taken to reduce the inter‐individual variability of plasma fatty acids levels. Using a cross‐over design, the subjects received 2.2 g of EPA in the first test period and 2.3 g of DHA in the second. The test periods were separated by 2 weeks. Blood samples were taken before dosing and after 2, 4, 6, 8, 12, 24, 48, and 72 h. The mean ± SE maximum concentrations for EPA were higher than for DHA (115 ± 11 μg/mL vs. 86 ± 12 μg/mL; p = 0.05). The mean ± SE incremented area under the plasma concentration curve over 72 h for EPA (2461 ± 279 μg/mL) was 2.4 times higher (p &lt; 0.001) than that for DHA (1021 ± 170 μg/mL). The mean ± SE half‐life was for EPA and DHA was 45 ± 8 and 66 ± 12 h. Our results indicate that EPA administration in single doses leads to higher circulating plasma levels of EPA compared to an effect of an equivalent dose of DHA on DHA plasma levels.

Associations between dietary fatty acid and plasma fatty acid composition in non-alcoholic fatty liver disease: secondary analysis from a randomised trial with a hypoenergetic low-carbohydrate high-fat and intermittent fasting diet.

Dietary fatty acids (FA) affect metabolic risk factors. The aim of this study was to explore if changes in dietary fat intake during energy restriction were associated with plasma FA composition. The study also investigated if these changes were associated with changes in liver fat, liver stiffness and plasma lipids among persons with non-alcoholic fatty liver disease. Dietary and plasma FA were investigated in patients with non-alcoholic fatty liver disease (n 48) previously enrolled in a 12-week-long open-label randomised controlled trial comparing two energy-restricted diets: a low-carbohydrate high-fat diet and intermittent fasting diet (5:2), to a control group. Self-reported 3 d food diaries were used for FA intake, and plasma FA composition was analysed using GC. Liver fat content and stiffness were measured by MRI and transient elastography. Changes in intake of total FA (r 0·41; P = 0·005), SFA (r 0·38; P = 0·011) and MUFA (r 0·42; P = 0·004) were associated with changes in liver stiffness. Changes in plasma SFA (r 0·32; P = 0·032) and C16 : 1n-7 (r 0·33; P = 0·028) were positively associated with changes in liver fat, while total n-6 PUFA (r -0·33; P = 0·028) and C20 : 4n-6 (r -0·42; P = 0·005) were inversely associated. Changes in dietary SFA, MUFA, cholesterol and C20:4 were positively associated with plasma total cholesterol and LDL-cholesterol. Modifying the composition of dietary fats during dietary interventions causes changes in the plasma FA profile in patients with non-alcoholic fatty liver disease. These changes are associated with changes in liver fat, stiffness, plasma cholesterol and TAG. Replacing SFA with PUFA may improve metabolic parameters in non-alcoholic fatty liver disease patients during weight loss treatment.

Plasma fatty acid levels and risk of non-small cell lung cancer: a large-scale prospective cohort study.

Non-small cell lung cancer (NSCLC) ranks among the most prevalent and lethal malignancies globally. Fatty acids (FAs) play a significant role in diverse physiological and pathological mechanisms, yet their precise involvement in NSCLC remains poorly understood. This study utilized a large-scale prospective cohort of 249,132 participants, observed over an average of 12 years, to investigate the relationship between different FAs and NSCLC risk. Analytical approaches included Cox proportional hazards regression, Kaplan-Meier survival analysis, accelerated failure time (AFT) modeling, and restricted cubic spline (RCS) analysis. During the follow-up period, 1,460 participants were diagnosed with NSCLC. Cox regression analysis demonstrated that elevated levels of docosahexaenoic acid (DHA), linoleic acid (LA), and omega-3 were inversely associated with NSCLC risk. Kaplan-Meier curves, along with AFT models, corroborated that elevated concentrations of DHA and LA significantly delayed NSCLC onset. Additionally, RCS analysis uncovered nuanced dose-response relationships between these FAs and NSCLC. Stratified analyses highlighted variability based on smoking status, gender, and body mass index subgroups. The concentration of specific FAs exhibits a significant association with NSCLC risk. These results offer a foundation for devising dietary FA composition adjustments aimed at reducing NSCLC risk.

PSIII-10 Flaxseed oil-based supplement alters water consumption and plasma fatty acid profile of beef heifers

Abstract The objective of this study was to determine the effects of a flaxseed oil-based supplement (FlaxLic, New Generations, SD) on reproductive parameters, feeding behavior, and lipid profile in beef heifers. Crossbred Angus heifers [n = 60 body weight (BW) = 397kg ± 5.2 kg) were blocked by BW and antral follicle count and randomly assigned to two supplementation treatments: free-choice commercial lose mineral supplement (CON; n = 30) or free-choice flaxseed oil-based supplement (FLAX; n = 30) for 7 wk. Heifers were individually fed via the Insentec feeding system (Insentec RIC, Hokofarm, Marknesse, Netherlands), where basal diet (TMR) and supplements were provided in separate feeders to measure supplement intake and feeding behavior. Further, water intake and behavior were measured via Insentec water system. Individual intake was compiled over 24 h for each animal. Body weight, transrectal ultrasonography, and blood samples were collected weekly. On wk 5, heifers were enrolled in a fixed-time artificial insemination (FTAI) commercial protocol. Largest follicle diameter (LF) and corpus luteum (CL) presence were recorded weekly and on d of the FTAI protocol (d 0, d 7, and d 0). Pregnancy diagnosis was performed 30 d and 60 d following AI. Blood samples were analyzed for progesterone (P4) by radioimmunoassay (RIA) to determine puberty attainment before wk 5, and fatty acid profile was determined via gas chromatography-flame ionization detection. Heifers with a CL or P4 ≤ 1.0 ng/mL were considered pubertal. Data were analyzed using SAS 9.4. ADG was similar between groups (P = 0.90) but was affected by week (P &amp;lt; 0.01). TMR intake was similar in duration and quantity (P &amp;gt; 0.18) between groups. Supplement intake was greater (P &amp;lt; 0.01) for FLAX (0.73 ± 0.03 kg/d) compared with CON (0.18 ± 0.02 kg/d) and from wk 2 to wk 8 (P = 0.01). Time spent consuming the supplements was greater for FLAX compared with CON heifers (62.65 ± 2.11 vs 0.10 ± 0.11 min/d, respectively) over the entire trial (P &amp;lt; 0.01). Further, FLAX heifers consumed less water than CON heifers (32.2 ± 0.39 vs 33.93 ± 0.35 kg/d, respectively; P = 0.03) and from wk 2 to wk 7 (P = 0.03). LF was not different between groups on any of the days of the protocol (d 0, d 7, d 0; P &amp;gt; 0.20). Additionally, P4 (P ≤ 0.20), puberty attainment by wk 5 (P = 0.24), and pregnancy rates (P &amp;gt; 0.48) were similar between groups. Concentrations of arachidonic acid (3.00 ± 0.24 vs 2.32 ± 0.19 mg/mL; P = 0.04), linoleic (60.11 ± 4.34 vs 40.35 ± 4.04 mg/mL; P = 0.002), αLinolenic (16.73 ± 0.26 vs 15.86 ± 0.23 mg/mL; P = 0.02), and total polyunsaturated fatty acids (PUFA; 130.52 ± 5.97 vs 111.19 ± 5.56 mg/mL; P = 0.02) were greater on wk 8 for FLAX compared with CON heifers. Collectively, these findings did not show evidence that the flaxseed oil-based supplement affects variables that impact reproductive performance. However, it altered the plasma lipid profile, increasing omega-3, arachidonic, and linoleic fatty acids, as well as total PUFA.

387 Impacts of rumen protected omega-6 fatty acid supplementation on cow reproduction and calf growth

Abstract Maternal nutrition during pregnancy is crucial for proper fetal development. Rumen protected omega-6 (ω-6) fatty acids (FA) may improve health and reproductive success in beef cattle. Previous research studied the effects of supplementing ω-6 on cow production either during late gestation or post-breeding but not during both stages. Our objective was to determine the effects of ω-6 supplementation during late gestation and post-breeding on cow reproduction and calf pre-weaning growth. Eighty cows were assigned to either a saturated FA control (C) or rumen protected ω-6 supplements for 40 d before parturition (PRE) and/or 35 d after artificial insemination (AI, POST) using a 2 × 2 factorial: PRE C-POST C(n = 19); PRE C-POST ω-6(n = 19); PRE ω-6-POST ω-6(n = 17); PRE ω-6-POST C(n = 18). Cows were fed ad libitum hay and water when on/off supplementation periods. Supplements were provided in low moisture tubs. Individual animal intake of supplement was measured by a GrowSafe system. Cow body weights and plasma FA concentrations were measured prior to and after supplementation during each period. Calves were weighed at birth, branding, 150 d old and weaning. Reproductive measurements included postpartum estrus activity, estrus response at fixed-time AI (FTAI), and pregnancy rates. Blood plasma for progesterone analysis was collected on d 7 post-AI on all cows. Corpus luteum (CL) area was measured on d 7 via transrectal ultrasonography on a subset of cows during the POST period (PRE ω-6-POST ω-6 n = 8; PRE C-POST C n = 8; PRE C-POST ω-6 n = 8; PRE ω-6-POST C n = 8). The relationship between supplement intake and plasma FA concentration was analyzed via linear regression, and all other variables were analyzed via ANOVA. Supplement intakes within treatments and between the PRE and POST supplemental periods were highly variable. Body weights remained similar for cows (P = 0.52), but POST ω-6 calves had larger weaning weights than POST C calves (P = 0.02). There was a positive linear relationship (r2 = 0.14, P &amp;lt; 0.03) between supplement intake and plasma FA for PRE ω-6 and POST ω-6. Positive linear relationships between intake and plasma ω-6 FA concentration were observed for PRE C (r2 = 0.11, P &amp;lt; 0.05), PRE ω-6 (r2 = 0.2, P &amp;lt; 0.007) and POST ω-6 (r2 = 0.31, P = 0.0005). Post-partum estrus activity was similar (P = 0.81) between PRE C and PRE ω-6 cows, and estrus response at FTAI was similar (P = 0.13) between POST C and POST ω-6 cows. POST ω-6 cows had larger CL areas than POST C cows (P = 0.03); however, blood progesterone concentrations at d 7 did not differ between treatments (P = 0.65). There was no difference in conception to FTAI between POST C and POST ω-6 (P = 0.08). These results indicate that free choice ω-6 FA supplementation during late gestation and post-AI result in large variation in intake between cows that influence plasma concentrations, but did not markedly alter reproductive measures in mature beef cows.

The association between plasma fatty acids and risk of lung cancer: a prospective cohort study of the UK Biobank.

Fatty acids (FAs) have emerged as significant contributors to tumorigenesis, yet prospective evidence regarding their specific effects on lung cancer risk remains scarce. To investigate the association between plasma FAs and lung cancer incidence, as well as a potential modification effect of genetic susceptibility on lung cancer risk. A cohort study was conducted involving 112,547 cancer-free participants from the UK Biobank, with measurements of plasma FAs, including saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) at baseline (2006-2010). Cox regression models were employed to assess lung cancer risk according to plasma FA quartiles or 1-SD increment. Furthermore, interaction between plasma FAs and polygenic risk score (PRS) was evaluated using an additive model. Over an average 10.9-year follow-up, 1122 lung cancer cases occurred. After multivariable adjustment, MUFAs were positively associated with lung cancer risk (hazard ratio [HR] per 1-SD = 1.32, 95% confidence interval [CI]: 1.13-1.54). In contrast, PUFAs, particularly n-3 PUFAs, n-6 PUFAs, docosahexaenoic acid, and linoleic acid, were associated with a lower risk of lung cancer, with HRs ranging from 0.79 (95% CI: 0.72-0.87) to 0.89 (95% CI: 0.83-0.95). SFAs were not significantly associated with lung cancer risk. Moreover, we observed an additive interaction between plasma PUFAs and genetic risk. Individuals with a high genetic risk and the lowest quartile of plasma PUFAs had the highest risk of lung cancer (HR = 2.20, 95% CI: 1.43-3.38). Our findings suggest that plasma PUFAs may serve as protective factors, while MUFAs represent risk factors for lung cancer, offering novel insights into lung cancer carcinogenesis and prevention.

Feeding intolerance after pediatric cardiac surgery is associated with dysbiosis, barrier dysfunction, and reduced short-chain fatty acids.

Congenital heart disease (CHD) is the most common birth defect, occurring in roughly 40,000 U.S. births annually. Malnutrition and feeding intolerance (FI) in CHD range from 30% to 42% and are associated with longer hospitalization and increased mortality. Cardiopulmonary bypass (CPB) required for surgical repair of CHD induces a systemic inflammatory response worsening intestinal dysbiosis and leading to intestinal epithelial barrier dysfunction (EBD), possibly contributing to postoperative FI. The objective of this study was to determine the relationship of postoperative FI with intestinal microbiome, short-chain fatty acids (SCFAs), and EBD in pediatric CHD after cardiac surgery. This was a prospective study of patients aged 0-15 years undergoing cardiac surgery with CPB. Samples were collected preoperatively and postoperatively to evaluate the gut microbiome, plasma EBD markers, short-chain fatty acids (SCFAs), and plasma cytokines. Clinical data were collected to calculate a FI score and evaluate patient status postoperatively. We enrolled 26 CPB patients and identified FI (n = 13). Patients with FI had unique microbial shifts with the reduced SCFA-producing organisms Rothia, Clostridium innocuum, and Intestinimonas. Patients who developed FI had associated elevations in the plasma EBD markers claudin-2 (P < 0.05), claudin-3 (P < 0.01), and fatty acid binding protein (P < 0.01). Patients with FI had reduced plasma and stool SCFAs. Mediation analysis showed the microbiome functional shift was associated with reductions in stool butyric and propionic acid in patients with FI. In conclusion, we provide novel evidence that intestinal dysbiosis, markers of EBD, and SCFA depletion are associated with FI. These data will help identify mechanisms and therapeutics to improve clinical outcomes following pediatric cardiac surgery.NEW & NOTEWORTHY Feeding intolerance contributes to postoperative morbidity following pediatric cardiac surgery. The intestinal microbiome and milieu play a vital role in gut function. Short-chain fatty acids are gut and cardioprotective metabolites produced by commensal bacteria and help maintain appropriate barrier function. Depletion of these metabolites and barrier dysfunction contribute to postoperative feeding intolerance following cardiac surgery. Identifying mechanistic targets to improve the intestinal milieu with the goal of improved nutrition and clinical outcomes is critical.

Abstract P381: Sex differences in association between gut microbiome and 24-hour blood pressure variability

Background: Blood pressure (BP) variability is an independent risk factor for cardiovascular disease (CVD). BP variability has been associated with cardiovascular organ damage and is a potential therapeutic target for the prevention of CVD. Recently, the gut microbiome (GM) has been shown to have a pathological role in hypertension, however, the association between GM and BP variability is poorly understood. Methods: 241 community-dwelling individuals free of symptomatic CVD from Hong Kong (113 males and 128 females, mean age 54±6 years) underwent ambulatory BP monitoring and stool microbiota shotgun sequencing. BP variability was determined as systolic/diastolic BP (SBP/DBP) coefficient of variation (CoV), nighttime dipping, and morning BP surge (MBPS). Sleep latency was estimated using 7-day Actigraphy data. Associations of BP variability with GM, and plasma and stool short-chain fatty acids (SCFAs) were analyzed under statistical models adjusting for age, sex, serum glucose and lipids, sodium intake assessed by urine analysis, menopause status, smoking, fatty liver, BP and sleep latency. Results: Women had a significantly higher 24-hour SBP ( p =0.0005) and DBP ( p =0.002) CoV than men. 24-hour SBP CoV had a negative association with GM α-diversity (Shannon and Simpson’s index: all P &lt;0.05) and a positive association with Firmicutes/Bacteroidetes ratio ( P &lt;0.05), suggesting gut dysbiosis in participants with higher systolic BP variability. Several GM species and SCFAs were significantly associated with the indices of BP variability in both men and women. Notably, Parabacteroides merdae had a negative association with both systolic and diastolic BP CoV (all P &lt;0.05-0.01). Bacteroidetes dorei and Bacteroides intestinalis were reduced in women with higher SBP CoV ( P &lt;0.05) and nondipping status ( P&lt; 0.01), respectively. Prewaking and sleepthrough MBPS had a positive association with Faecalibacterium prausnitzii in women (all P &lt;0.001) and plasma acetic acid levels in men ( P &lt;0.05-0.001). Further analysis indicated that Bacteroidetes dorei may mediate SBP CoV via plasma iso-butyric acid in women (bootstrapping 95% CI: -3.6 to -0.19; P &lt;0.05). Conclusions: This cross-sectional study suggests sex-specific associations between GM and BP variability. Most noteworthy, higher systolic BP variability was associated with a significant reduction in potentially beneficial bacterial species, primarily in women which may be explored for therapeutic potential.

Cold-induced phosphatidylethanolamine synthesis in liver and brown adipose tissue of mice

Increasing energy expenditure in brown adipose (BAT) tissue by cold-induced lipolysis is discussed as a potential strategy to counteract imbalanced lipid homeostasis caused through unhealthy lifestyle and cardiometabolic disease. Yet, it is largely unclear how liberated fatty acids (FA) are metabolized. We investigated the liver and BAT lipidome of mice housed for 1 week at thermoneutrality, 23 °C and 4 °C using quantitative mass spectrometry-based lipidomics. Housing at temperatures below thermoneutrality triggered the generation of phosphatidylethanolamine (PE) in both tissues. Particularly, the concentrations of PE containing polyunsaturated fatty acids (PUFA) in their acyl chains like PE 18:0_20:4 were increased at cold. Investigation of the plasma's FA profile using gas chromatography coupled to mass spectrometry revealed a negative correlation of PUFA with unsaturated PE in liver and BAT indicating a flux of FA from the circulation into these tissues. Beta-adrenergic stimulation elevated intracellular levels of PE 38:4 and PE 40:6 in beige wildtype adipocytes, but not in adipose triglyceride lipase (ATGL)-deficient cells. These results imply an induction of PE synthesis in liver, BAT and thermogenic adipocytes after activation of the beta-adrenergic signaling cascade.

Crucial Interactions between Altered Plasma Trace Elements and Fatty Acids Unbalance Ratio to Management of Systemic Arterial Hypertension in Diabetic Patients: Focus on Endothelial Dysfunction.

The coexistence of SAH with T2DM is a common comorbidity. In this study, we investigated the link between altered plasma antioxidant trace elements (ATE: manganese, selenium, zinc, and copper) and fatty acids ratio (FAR: polyunsaturated/saturated) imbalance as transition biomarkers between vascular pathology (SAH) to metabolic pathology (T2DM). Our data revealed strong correlation between plasma ATE and FAR profile, which is modified during SAH-T2DM association compared to the healthy group. This relationship is mediated by lipotoxicity (simultaneously prominent visceral adipose tissue lipolysis, significant flow of non-esterified free fatty acids release, TG-Chol-dyslipidemia, high association of total SFA, palmitic acid, arachidonic acid, and PUFA ω6/PUFA ω3; drop in tandem of PUFA/SFA and EPA + DHA); oxidative stress (lipid peroxidation confirmed by TAS depletion and MDA rise, concurrent drop of Zn/Cu-SOD, GPx, GSH, Se, Zn, Se/Mn, Zn/Cu; concomitant enhancement of Cu, Mn, and Fe); endothelial dysfunction (endotheline-1 increase); athero-thrombogenesis risk (concomitant rise of ApoB100/ApoA1, Ox-LDL, tHcy, and Lp(a)), and inflammation (higher of Hs-CRP, fibrinogen and ferritin). Our study opens to new therapeutic targets and to better dietary management, such as to establishing dietary ATE and PUFA ω6/PUFA ω3 or PUFA/SFA reference values for atherosclerotic risk prevention in hypertensive/diabetic patients.

Zexie-Baizhu Decoction ameliorates non-alcoholic fatty liver disease through gut-adipose tissue crosstalk

Ethnopharmacological relevanceZexie-Baizhu Decoction (AA), a Chinese Classical Formula composed of Alisma orientalis (Sam.) Juzep. and Aractylodes Macrocephala Koidz in the specific ratio of 5:2, has a long history of use in treating metabolic disorders. Recent studies have demonstrated AA's ameliorative effects on non-alcoholic fatty liver disease (NAFLD); however, the mechanism underlying its action on the gut and adipose tissue, key regulators of metabolism, have not been fully explored. Aim of the studyThis study aimed to investigate the mechanisms by which AA regulates the homeostasis of gut and adipose tissue in NAFLD. Materials and methodsAA (1500 mg/kg/day) or vehicle was administrated to the high-fat diet-induced and normal chow-fed mice (C57BL/6J). Plasma, the liver, gut microbiota, bile acids, and short-chain fatty acids in the gut, were systematically investigated. RNA sequencing analysis, reverse transcription quantitative real-time PCR, and Western Blotting were performed on the epididymal white adipose tissues (eWAT) to explore AA's influence on NAFLD. Lipidomics of the liver and eWAT were analyzed by liquid chromatography-mass spectrometry and desorption electrospray ionization mass spectrometry imaging. ResultsOur study demonstrated that AA administration effectively alleviated liver injury induced by NAFLD, as evidenced by reduced hepatic fat accumulation and inflammation. Mechanistically, AA modulated the composition of the gut microbiota, promoting the growth of beneficial bacteria such as Akkermansia muciniphila and restoring the balance between Firmicutes and Bacteroidetes. Furthermore, AA regulated the levels of bile acids and short-chain fatty acids in the intestine, plasma, and liver. Correspondingly in the eWAT, AA administration activated bile acid receptor (Gpbar1) and short-chain fatty acid receptor (Ffar2), facilitating lipid breakdown and attenuating triglyceride accumulation. Transcriptome analysis revealed that AA influenced gene expression related to fatty acid metabolism, thermogenesis, insulin resistance, AMPK signaling, and the tricarboxylic acid (TCA) cycle, thereby improving NAFLD at the transcriptional level. Additionally, AA treatment significantly altered the lipid composition in the liver, reducing levels of diacylglycerols, triacylglycerols, phosphatidylserines, and cholesterol esters, while increasing levels of phosphatidic acids, phosphatidylethanolamines, and sphingomyelins. ConclusionOur study builds a connection between the gut and adipose tissue to understand the mechanism of AA on alleviating NAFLD, providing new insights into the development of targeted therapies for this condition.