Plasma Levels Of Fatty Acids Research Articles

Palmitoleic and oleic fatty acids as biomarkers for coronary heart disease: A predictive model.

saturated and unsaturated fatty acid showed a significant link with coronary artery health and disease. This study aimed to compare plasma levels of unsaturated fatty acids (UFAs) between individuals with coronary heart disease (CHD) and those without. It also investigated the association between specific UFA ratios and the presence or severity of acute coronary syndrome (ACS). Additionally, the study explored the potential of UFAs as biomarkers for assessing CHD risk or disease severity. Patients suspected of coronary heart disease (CHD) at Northern Jiangsu People's Hospital were categorized by coronary angiography into non-CHD (53 cases) and CHD (182 cases). The CHD group was divided into non-acute coronary syndrome (non-ACS) (40 cases) and ACS (142 cases) subgroups. The ACS group was further classified into unstable angina (61 cases), non-ST-elevation myocardial infarction (NSTEMI) (40 cases), and ST-elevation myocardial infarction (STEMI) (41 cases). Lipid profiles, myocardial injury markers, and fourteen unsaturated fatty acids were analyzed using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The CHD group had significantly higher triglycerides (TG), palmitoleic acid (PA), oleic acid (OA), docosahexaenoic acid (DHA), ω-6 fatty acids, and a higher ω-6/ω-3 ratio, but lower ω-3 fatty acids compared to non-CHD. In ACS, PA, LA, OA, and the ω-6/ω-3 ratio were elevated, while EPA and HDL were reduced. Logistic regression identified TG, ω-6/ω-3 ratio, PA, OA, and ω-6 fatty acids as risk factors, with ω-3 fatty acids being protective. PA was protective, while OA posed risk. A combined PA and OA model had a diagnostic efficacy (AUC 0.746). Altered fatty acid metabolism in CHD patients, particularly PA and OA, offers potential as biomarkers. The ω-6/ω-3 ratio is crucial for cardiovascular health.

Supplementation and Mitigating Cognitive Decline in Older Adults With or Without Mild Cognitive Impairment or Dementia: A Systematic Review.

This systematic literature review aims to answer the question of how micronutrients might influence the development and progression of dementia. In the present work, we focused on an overview of an updated review of relevant literature published in the last two decades. This review aims to delineate the relationship between micronutrient supplementation and cognitive decline in older subjects. In carrying out this review, we followed PRISMA, and our literature search was performed on PubMed. This systematic review includes only primary studies that have investigated the efficacy of nutritional interventions for the prevention of dementia and improvement of cognitive function in subjects aged 65 years or older with normal cognition, mild cognitive impairment (MCI), or Alzheimer's disease (AD). A gross heterogeneity of studies forbids the possibility of a direct comparison of the results. A review of the inclusion criteria and restrictions has been conducted to check the validity and reliability of the results. In this review, thirty-three primary studies were included. Results have shown that supplementation with vitamin D, probiotics, and PUFAs would most likely reduce cognitive decline, dementia, or AD compared with vitamins A, B, C, and E, which were seen to be relatively ineffective. Of note, when considering vitamin B supplementation, positive effects were only observed in non-aspirin users having high ω-3 fatty acid (ω-3 FA) plasma levels. In some cases, however, there were genotypic differences in subjects in response to vitamin B supplementation.

Plasma levels of polyunsaturated fatty acids and multiple sclerosis susceptibility in a US case-control study

BackgroundThere are plausible mechanisms, yet mixed evidence, that higher polyunsaturated fatty acids (PUFAs) levels reduces the risk of multiple sclerosis (MS). Prior studies relied on dietary surveys to estimate levels. ObjectiveWe tested associations between plasma levels of n-3 and n-6 PUFAs and likelihood of MS onset or clinically isolated syndrome (CIS) using data from the MS Sunshine Study, a case-control study conducted in the United States. MethodsCase participants (n = 589) aged ≥ 18 years and matched control participants (n = 630) were recruited between 2011 and 2015. Plasma phospholipid fatty acid profiling was conducted by gas-liquid chromatography. We used logistic regression to report odds ratios, testing for interactions, adjusting for covariates and correcting for multiple comparisons. ResultsThere was a 6 % lower probability of MS/CIS per unit increase in total n-6 PUFA level, expressed as a percentage of total plasma phospholipid fatty acids (odds ratio = 0.94; 95 % confidence interval = 0.90,0.98; p = 0.012). We found no statistically significant association between individual or total plasma levels of n-3 PUFAs and probability of MS/CIS; however, plasma levels of n-3 PUFAs were low across the cohort. No other individual or aggregate PUFA levels were significantly associated with MS/CIS. ConclusionA higher total n-6 PUFA level may be beneficial in terms of MS susceptibility.Further research is needed to determine whether n-3 PUFAs may be beneficial only above a threshold that is achievable by supplementation.

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 < 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.

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.

Rice Protein Reduces Triglyceride Levels through Modulating CD36, MTP, FATP, and FABP Expression in Growing and Adult Rats.

To elucidate the effect of rice protein on the regulation of triglyceride transport to reduce triglyceride levels, growing and adult male Wistar rats were fed with casein and rice protein for 2 weeks. With the intake of rice protein, the gene and protein expressions of cluster determinant 36 (CD36), microsomal triglyceride transfer protein (MTP), fatty acid transport protein-2 (FATP-2), and fatty acid-binding protein-1 (FABP-1) were, respectively, downregulated in growing and adult rats, suggesting rice protein could effectively regulate triglyceride transport. As a result, rice protein significantly reduced plasma levels of triglyceride and fatty acids, while hepatic accumulations of triglyceride and fatty acids were also decreased via rice protein. The present study demonstrates that RP exerts regulatory effects on CD36, MTP, FATP-2, and FABP-1 expression in growing and adult rats, revealing a link to triglyceride-lowering actions and the modulations of triglyceride transport exerted by rice protein. Results suggest that the aging process cannot attenuate the depression of CD36, MTP, FATP, and FABP 19 expression to reduce triglyceride levels induced by rice protein.

Association of maternal blood and umbilical cord blood plasma fatty acid levels with the body size at birth of Japanese infants

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mainly obtained from fish, have been implicated in fetal development. Because few studies have examined maternal and umbilical cord blood fatty acid levels and infant body size in Japan with a fish-eating culture, we examined differences in plasma fatty acid levels in pregnant women and infant size at birth. This study is a large birth cohort study of 1476 pairs of Japanese pregnant women and their infants. Maternal blood DHA levels and infant birth weight showed a positive relationship. However, analysis adjusted for gestational age did not reveal correlations. Negative relationships were found between cord blood DHA levels and infant body size, and between the difference in mother-to-child DHA levels and infant body size. Thus, the smaller the birth size, the higher the differences in umbilical cord blood DHA levels and mother-to-child DHA levels when considering gestational age.

Oral exposure to bisphenol S is associated with alterations in the oviduct proteome of an ovine model, with aggravated effects in overfed females

BackgroundBisphenol S (BPS) is a substitute for bisphenol A in plastic manufacturing and, as a potential endocrine disruptor, may alter the physiology of the oviduct, in which fertilization and early embryo development take place in mammals. The objective of this study was to assess the effect of a daily dietary exposure to BPS combined with a contrasted diet on the oviduct fluid proteome using an ovine model.ResultsEighty adult cyclic ewes were allotted to four groups (20/group): overfed (OF) consuming 50 µg/kg/day of BPS in their diet, underfed (UF) consuming 50 µg/kg/day of BPS, and non-exposed controls in each diet group. After three months, the mean body condition score, plasma levels of glucose and non-esterified fatty acids were significantly higher in OF than in UF females. The proteins in collected OF samples (50 µg) were analyzed by nanoliquid chromatography coupled with tandem mass spectrometry (nanoLC-MS/MS). Overall, 1563 proteins were identified, among which 848 were quantified. Principal component analysis of the data revealed a clear discrimination of samples according to the diet and a segregation between BPS-exposed and non-exposed females in overfed ewes. Hierarchical clustering of differentially abundant proteins (DAPs) identified two clusters of 101 and 78 DAPs according to the diet. Pairwise comparisons between groups revealed a stronger effect of BPS in OF than in UF females (70 vs. 24 DAPs) and a stronger effect of the diet in BPS-exposed than non-exposed females (56 vs. 36 DAPs). Functional analysis of DAPs showed an enrichment in metabolic processes, immune system, cell response to stress, and reproductive processes.ConclusionsThis work highlights for the first time the important impact of BPS on the oviduct proteome, with larger effects seen in OF than UF females. These results, together with previous ones, raise health concerns for everyone and call for a greater regulation of BPS in the food industry.

Effective reduction in seizure severity and prevention of a fatty liver by a novel low ratio ketogenic diet composition in the rapid kindling rat model of epileptogenesis

Drug-resistant epilepsy patients may benefit from non-pharmacological therapies, such as the ketogenic diet (KD). However, its high fat content poses compliance challenges and metabolic risks. To mitigate this, we developed a novel KD composition with less fat and additional nutrients (citrate, nicotinamide riboside, and omega-3 fatty acids) for ketone-independent neuroprotection. The efficacy, metabolic and neuropathological effects of the novel KD and a classic KD were compared to a control diet in the rapid kindling model of temporal lobe epilepsy. Both KD groups entered ketosis before kindling onset, with higher ketone levels in the classic KD group. Remarkably, rats on the novel KD had slower progression of behavioral seizures as compared to rats on a control diet, while this was not the case for rats on a classic KD. Both KDs reduced electrographic after-discharge duration, preserved neurons in the dorsal hippocampus, and normalized activity in open field tests. The novel KD, despite lower fat and ketone levels, demonstrated effective reduction of behavioral seizure severity while the classic KD did not, suggesting alternative mode(s) of action are involved. Additionally, the novel KD significantly mitigated liver triglyceride and plasma fatty acid levels compared to the classic KD, indicating a reduced risk of long-term liver steatosis. Our findings highlight the potential of the novel KD to enhance therapeutic efficacy and compliance in epilepsy patients.

Limosilactobacillus reuteri DSM 17938 relieves inflammation, endoplasmic reticulum stress, and autophagy in hippocampus of western diet-fed rats by modulation of systemic inflammation.

The consumption of western diets, high in fats and sugars, is a crucial contributor to brain molecular alterations, cognitive dysfunction and neurodegenerative diseases. Therefore, a mandatory challenge is the individuation of strategies capable of preventing diet-induced impairment of brain physiology. A promising strategy might consist in the administration of probiotics that are known to influence brain function via the gut-brain axis. In this study, we explored whether Limosilactobacillus reuteri DSM 17938 (L. reuteri)-based approach can counteract diet-induced neuroinflammation, endoplasmic reticulum stress (ERS), and autophagy in hippocampus, an area involved in learning and memory, in rat fed a high fat and fructose diet. The western diet induced a microbiota reshaping, but L. reuteri neither modulated this change, nor the plasma levels of short-chain fatty acids. Interestingly, pro-inflammatory signaling pathway activation (increased NFkB phosphorylation, raised amounts of toll-like receptor-4, tumor necrosis factor-alpha, interleukin-6, GFAP, and Haptoglobin), as well as activation of ERS (increased PERK and eif2α phosphorylation, higher C/EBP-homologous protein amounts) and autophagy (increased beclin, P62-sequestosome-1, and LC3 II) was revealed in hippocampus of western diet fed rats. All these hippocampal alterations were prevented by L. reuteri administration, showing for the first time a neuroprotective role of this specific probiotic strain, mainly attributable to its ability to regulate western diet-induced metabolic endotoxemia and systemic inflammation, as decreased levels of lipopolysaccharide, plasma cytokines, and adipokines were also found. Therapeutic strategies based on the use of L. reuteri DSM17938 could be beneficial in reversing metabolic syndrome-mediated brain dysfunction and cognitive decline.

Circulating fatty acids and risk of hepatocellular carcinoma and chronic liver disease mortality in the UK Biobank

Nuclear magnetic resonance (NMR)-based plasma fatty acids are objective biomarkers of many diseases. Herein, we aim to explore the associations of NMR-based plasma fatty acids with the risk of hepatocellular carcinoma (HCC) and chronic liver disease (CLD) mortality in 252,398 UK Biobank participants. Here we show plasma levels of n-3 poly-unsaturated fatty acids (PUFA) and n-6 PUFA are negatively associated with the risk of incident HCC [HRQ4vsQ1: 0.48 (95% CI: 0.33–0.69) and 0.48 (95% CI: 0.28–0.81), respectively] and CLD mortality [HRQ4vsQ1: 0.21 (95% CI: 0.13–0.33) and 0.15 (95% CI: 0.08–0.30), respectively], whereas plasma levels of saturated fatty acids are positively associated with these outcomes [HRQ4vsQ1: 3.55 (95% CI: 2.25–5.61) for HCC and 6.34 (95% CI: 3.68–10.92) for CLD mortality]. Furthermore, fibrosis stage significantly modifies the associations between PUFA and CLD mortality. This study contributes to the limited prospective evidence on the associations between plasma-specific fatty acids and end-stage liver outcomes.

Positive effects of low-dose S-ketamine on preventing myocardial injury after thoracoscopic lobectomy in patients aged 70 to 85

ObjectiveTo investigate the effects of low-dose S-ketamine on marker of myocardial injury (BNP, hs-cTnT and HFABP) after thoracoscopic lobectomy in patients aged 70 to 85.MethodsOne hundred patients (four cases excluded) aged 70–85 years, with body mass index 18–24 kg·m−2 and American Society of Anesthesiologists physical status II–III, scheduled for elective lobectomy from April 2022 to April 2023, were selected. The patients were divided into two groups by a random number table method, namely, the low-dose S-ketamine combined with GDFT group (group S) and the control group (group C), with 48 cases in each group. In group S, a low dose of S-ketamine (0.2 mg/kg) was given 1 min before intubation, and the maintenance dose was 0.12 mg·kg−1·h−1. Fluid therapy, guided by cardiac index (CI), changes in stroke volume (△SV), and other dynamic indicators, was used for rehydration during the operation. Group C was given the same amount of normal saline (0.2 mg/kg) 1 min before intubation, and the same rehydration therapy was adopted during the operation. The mean arterial pressure (MAP) and heart rate (HR) of the two groups were observed and recorded immediately after entering the operating room (T0), immediately after intubation (T1), immediately after the beginning of one-lung ventilation (OLV) (T2), immediately after the beginning of surgery (T3), immediately after the end of OLV (T4), and at the end of surgery (T5). The intraoperative fluid intake and output and the use of vasoactive drugs were recorded. The plasma levels of heart-type fatty acid–binding protein (HFABP), high-sensitivity troponin T (hs-cTnT), brain natriuretic peptide (BNP), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were recorded 24 h before operation and 24 and 48 h after operation. Visual analogue scale (VAS) pain scores at rest were recorded at 2 (V1), 6 (V2), 12 (V3), 24 (V4), and 48 h (V5) after operation, and the occurrence of myocardial ischemia during hospitalization was noted.ResultsCompared with group C, MAP was significantly higher at T1–T5 in group S (P < 0.05), and the plasma concentrations of IL-6, IL-8, TNF-α, BNP, hs-cTnT, and HFABP were significantly lower at 24 and 48 h after operation (P < 0.05). The VAS pain scores at 2, 6, 12, 24, and 48 h after operation, the number of effective patient-controlled intravenous analgesia (PCIA) compressions, and the total number of PCIA compressions within 48 h after operation were significantly decreased (P < 0.05). Compared with group C, The hospitalization days, and the incidence of postoperative myocardial ischemia in group S were lower (P < 0.05). There were no significant intergroup differences in urine volume, extubation time, the incidence of postoperative atrial fibrillation, bleeding volume, colloid infusion volume, total fluid infusion volume, and the incidence of rescue analgesia.ConclusionsLow-dose S-ketamine can reduce the levels of hs-cTnT, HFABP, and BNP in older patients after pulmonary lobectomy, which has a positive effect on preventing myocardial injury.Trial registrationThis study was registered on CHICTR (registration No. ChiCTR2300074475). Date of registration: 08/08/2023.

Plasma Levels of Polyunsaturated Fatty Acids and Adverse Kidney Outcomes

Many studies have reported polyunsaturated fatty acids (PUFA) as significant predictors of cardiovascular disease, but little is known about the relationship between PUFA levels and chronic kidney disease (CKD). This study explored this relationship among individuals with and without CKD. Prospective observational cohort study. 73,419 participants without CKD (cohort 1) and 6,735 participants with CKD (cohort 2) in the UK Biobank Study, with PUFA levels measured between 2007 and2010. Percentage of plasma PUFA, omega-3 fatty acid (FA), omega-6 FA, docosahexaenoic acid (DHA), and linoleic acid relative to total FA. Incident CKD for cohort 1 and incident kidney failure requiring replacement therapy (KFRT) for cohort2. Cox proportional hazards regression analyses, including a cause-specific competing risk model. In cohort 1, individuals with higher quartiles of plasma PUFA levels had healthier lifestyles and fewer comorbidities. During 841,007 person-years of follow-up (median 11.9 years), incident CKD occurred in 4.5% of participants (incidence rate, 39.1 per 10,000 person-years). For incident CKD in cohort 1, the adjusted cause-specific hazard ratios for quartiles 2, 3, and 4 were 0.83 (95% CI, 0.75-0.92), 0.85 (95% CI, 0.76-0.96), 0.71 (95% CI, 0.62-0.82), respectively, compared with quartile 1. This inverse relationship was consistently observed for all PUFA types. In cohort 2, although total PUFA levels were not associated with KFRT, higher PUFA subtype levels of DHA were associated with a lower risk of KFRT. Observational design and limited generalizability to individuals with higher disease severity; no data on eicosapentaenoic acid. Among individuals without CKD, higher plasma PUFA levels and all 4 PUFA components were associated with a lower risk of incident CKD. In individuals with CKD, only the omega-3 component of PUFA, DHA, was associated with a lower risk of KFRT. Low amounts of polyunsaturated fatty acids (PUFA) in the blood are suspected of increasing the chances of heart disease, but it is not known whether the PUFA relates to kidney disease occurrence. In a large group without kidney disease in the United Kingdom, people with higher levels of PUFA in their blood tended to have a lower risk of developing kidney disease compared to those with lower PUFA levels. This relationship was consistently observed for all PUFA types. However, in the group with kidney disease, only higher levels of docosahexaenoic acid, a subtype of PUFAs, were associated with a lower risk of developing severe kidney problems that required kidney replacement therapy. These findings suggest that higher levels of PUFA, found in certain healthy fats, might protect against the development of kidney disease in the general population. As kidney function declines, only the docosahexaenoic acid, a subtype of PUFA, appears to be associated with preserved kidney function.

B-GOS alleviates olanzapine-induced lipid disturbances in mice by enriching Akkermansia and upregulation of PGRMC1-Wnt signaling

Although olanzapine (OLZ) remains one of the most efficacious antipsychotic medications for the treatment of schizophrenia, there are significant tolerability issues related to its metabolic profile such as weight gain and dyslipidemia. Our previous studies have demonstrated that progesterone receptor membrane component 1 (PGRMC1) plays a key role in antipsychotic-induced metabolic side effects. Prebiotics showed positive effects on lipid metabolism, however, limited studies focused on their therapeutic potential and mechanisms in treating antipsychotic-induced lipid metabolic disorders. Herein, our study aims to explore the effects of the prebiotic B-GOS on lipid disturbances induced by OLZ and elucidate its underlying mechanisms via PGRMC1 pathway. In an 8-week study, long-term intraperitoneal administration of OLZ at a dosage of 8 mg/kg/day in mice induced lipid disturbances as manifested by significantly increased lipid indexes in plasma and liver. B-GOS effectively alleviated the OLZ-induced abnormal lipid metabolism by enhancing the diversity of the gut microbiota, with a 100-fold increase in Akkermansia abundance and a 10-fold decrease in Faecalibaculum abundance. Followed by the B-GOS related changes of gut microbiota, OLZ-induced substantial hepatic inhibition of PGRMC1, and associated protein factors of Wnt signaling pathway (Wnt3a, β-catenin, and PPAR-γ) were reversed without affecting plasma levels of short-chain fatty acids. Taken together, prebiotics like B-GOS enriching Akkermansia offer a promising novel approach to alleviate antipsychotic-induced lipid disturbances by modulating the PGRMC1-Wnt signaling pathway.

Essential Fatty Acid Associated with Heart Rate Variability in Highly Trained Male Cross-Country Skiers: A Pilot Study

Polyunsaturated fatty acid (PUFA) metabolites play important roles in the modulation of vascular tone, heart rate variability (HRV), and cardiovascular diseases. This study was undertaken to examine the relationship between HRV and the plasma levels of essential acids. Methods: Highly trained cross-country skiers participated in the study (n = 19). Time-domain and frequency-domain HRV analyses were performed. The plasma levels of fatty acids were determined using gas–liquid chromatography. Results: Plasma eicosapentaenoic acid and docosahexaenoic acid were found to be negatively correlated with resting heart rate (HR) (p = 0.026). The plasma levels of alpha-linolenic acid (ALA) were positively associated with the relative value of high-frequency power (rs = 0.465, p = 0.045) and negatively correlated with the sympathovagal balance ratio (rs = −0.493, p = 0.032) and the absolute and relative values of low-frequency power (rs = −0.490, p = 0.028). The plasma levels of arachidonic acid (ARA) were positively associated with the relative value of high-frequency power (rs = 0.59, p = 0.006) and negatively correlated with the sympathovagal balance ratio (rs = −0.54, p = 0.017) and the relative values of low-frequency power (rs = −0.52, p = 0.022). No correlation was found between n6/n3 and HRV parameters except for HR and pNN50. Conclusions: n-3 PUFAs and ARA play an important role in the autonomic regulation of heart rate in highly trained skiers. Athletes with substantial deficiencies in plasma ALA and excess levels of ARA had increased sympathetic and decreased parasympathetic activity.

Abstract A057: Decreased plasma linoleic acid and increased oleic acid associated with obesity in pancreatic cancer

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy that interferes with absorption of nutrients including fats. Obesity is a key risk factor for PDAC and confers metabolic dysfunction associated with changes in fatty acid (FA) metabolism, including FAs in the linoleic acid and palmitic acid pathways. In turn, FAs can influence the molecular signaling in pancreatic cells. Changes in blood FA abundance induced by PDAC could be amplified by obesity and influence PDAC-associated outcomes. Therefore, we investigated plasma FA abundance in patients with treatment-naïve PDAC compared with control participants and explored how obesity status affects the linoleic acid and palmitic acid pathways in cancer. Methods: Blood and clinical characteristics were collected from participants with resectable tumors (rPDAC, n=52) or metastatic disease (mPDAC, r=55) that were treatment-naïve and 22 controls. Plasma samples were analyzed for relative FA abundance using gas chromatography and levels were compared between controls, rPDAC and mPDAC. Changes in FA abundance due to obesity (body mass index ≥30 kg/m2) were assessed in all groups. All FA abundance changes were analyzed using a two-way ANOVA with the appropriate parametric or non-parametric test, and p-values were adjusted using the Bonferroni correction. Results: Compared with controls, both rPDAC and mPDAC were associated with increased FA abundance of palmitic acid and decreased abundance of linoleic acid, γ-linolenic acid, and dihomo-γ-linolenic acid, regardless of obesity status (p&amp;lt;0.05). Plasma FA abundance of linoleic acid was increased in mPDAC versus rPDAC, regardless of obesity status (p&amp;lt;0.05). Decreased abundance of linoleic acid was noted in rPDAC and mPDAC participants with obesity versus participants without obesity, while there was an increased abundance of oleic acid observed in mPDAC among participants with obesity versus participants without obesity (p&amp;lt;0.05). Conclusions: Plasma FA levels are dysregulated in all PDAC stages versus controls. The results suggest that obesity-associated metabolic dysregulation influences linoleic acid and oleic acid abundances of participants with treatment-naïve PDAC. By improving our understanding of how obesity influences FA abundance in PDAC, we can identify novel mechanistic targets for treatment specific to PDAC stage and obesity status. Citation Format: Kaylin M. Chasser, Martha A. Belury, Jordan M. Cloyd, Rachel M. Cole, Stacey Culp, Mary E. Dillhoff, Aslam Ejaz, Kristyn Gumpper-Fedus, Phil A. Hart, Lauren Kanzaki, Andrei V. Manilchuk, Anne M. Noonan, Timothy M. Pawlik, Mitchell Ramsey, Zobeida Cruz-Monserrate. Decreased plasma linoleic acid and increased oleic acid associated with obesity in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A057.

High linoleic acid levels in red blood cells predict a poor response to neoadjuvant chemotherapy in human epidermal growth factor receptor type 2-positive breast cancer patients

ObjectivePolyunsaturated fatty acids are categorized as ω-3 or ⍵-6. Previous studies demonstrate that breast cancers display a high expression of fatty acid synthase and high fatty acid levels. Our study sought to determine if changes in plasma or red blood cell membrane fatty acid levels were associated with the response to preoperative (neoadjuvant) chemotherapy in non-metastatic breast cancer patients. MethodsOur prospective study assessed fatty acid levels in plasma and red blood cell membrane. Response to neoadjuvant chemotherapy was evaluated by the presence or absence of pathologic complete response and/or residual cancer burden. ResultsA total of 28 patients were included. First, patients who achieved pathologic complete response had significantly higher neutrophil-to-lymphocyte ratio versus no pathologic complete response (P = 0.003). Second, total red blood cell membrane polyunsaturated fatty acids were higher in the absence of pathologic complete response (P = 0.0028). Third, total red blood cell membrane ⍵-6 polyunsaturated fatty acids were also higher in no pathologic complete response (P < 0.01). Among ⍵-6 polyunsaturated fatty acids, red blood cell membrane linoleic acid was higher in the absence of pathologic complete response (P < 0.01). Notably, plasma polyunsaturated fatty acid, ⍵-6, and linoleic acid levels did not have significant differences. A multivariate analysis confirmed red blood cell membrane linoleic acid was associated with no pathologic complete response; this was further confirmed by receiver operating characteristic analysis (specificity = 92.3%, sensitivity = 76.9%, and area under the curve = 0.855). ConclusionsPending further validation, red blood cell membrane linoleic acid might serve as a predictor biomarker of poorer response to neoadjuvant chemotherapy in non-metastatic human epidermal growth factor receptor type 2–positive breast cancer. Measuring fatty acids in red blood cell membrane could offer a convenient, minimally invasive strategy to identifying patients more likely to respond or those with chemoresistance.

Cardiovascular and metabolic effects of MANP. a novel GC-A activator, in human hypertension with metabolic syndrome

Abstract Background/Introduction Hypertension (HTN) and metabolic syndrome (MetS) are both leading risk factors for major cardiovascular diseases, which frequently coexist as a complicated cardiometabolic disorder. The cardiac hormone atrial natriuretic peptide (ANP) plays a key role in both blood pressure and metabolic regulation through activation of the guanylyl cyclase-A receptor (GC-A) and the second messenger 3’,5’ cyclic guanosine monophosphate (cGMP). Indeed, ANP decreases blood pressure, induces lipolysis by increasing plasma levels of non-esterified fatty acids (NEFA) and improves insulin-sensitivity. MANP is a new Mayo Clinic designed natriuretic peptide consisting of the native ANP with a 12-amino-acid C-terminus extension and its biological actions are mediated by the GC-A/cGMP pathway. MANP is less susceptible to neprilysin degradation and exert more sustained cGMP dependent biological actions than ANP. Purpose In a proof-of-principle human study, for the first time we aimed to determine the cardiovascular and metabolic properties of MANP, a novel ANP analog, in the clinical setting of HTN with MetS. Methods We conducted a double-blind, placebo-controlled trial in 22 patients (17 receiving MANP) with HTN and MetS involving single subcutaneous injection of MANP (2.5 µg/kg) or placebo (NCT03781739). Blood pressure (BP) and circulating cGMP were monitored for 24 hours post treatment. Circulating metabolic parameters including insulin, glucose, non-esterified fatty acids (NEFA) and insulin resistance (HOMA-IR) and insulin sensitivity (HOMA-IS) indexes were assessed for the first 4 hours post treatment. Results Compared to baseline, MANP increased plasma cGMP at 30 minutes (delta: 4.8 ± 2.0 pmol/mL, P = 0.02) and 1 hour (delta: 2.9 ± 1.3 pmol/mL, P = 0.03) post injection. At 6 hours, systolic BP decreased by 5.7 ± 2.9 mmHg (P = 0.06) in the MANP group, whereas no reduction in BP was observed in placebo group. Among the 17 subjects receiving MANP, lower baseline cGMP levels were associated with greater mean reductions in systolic BP (ρ = 0.66, P = 0.005). After MANP injection, glucose levels decreased at 2 (delta: -4.7 ± 2.1 mg/mL, P = 0.04) and 4 hours (delta: -13.1 ± 3.9 mg/mL, P = 0.003) compared to baseline while insulin levels remained stable. During the first 4 hours post injection, we also observed a trend of increase in insulin sensitivity index (HOMA2-IS) and decrease in insulin resistance index (HOMA2-IR) with MANP, both were opposite to the trends in placebo. At 1 hour post MANP administration, NEFA increased by 108.2 ± 37.4 µM compared to baseline (P = 0.01). Conclusion(s) Our findings support the favorable cardiovascular and metabolic actions of MANP as a potential therapeutic strategy for HTN with MetS.

Human blood lipid profiles after dietary supplementation of different omega 3 ethyl esters formulations

The validity of omega 3 fatty acids (ω3 FAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as dietary supplements has been widely proved. It’s well known in fact, that they protect against cardiovascular diseases, reduce the levels of triacylglycerides (TAGs) and cholesteryl esters (CEs) in blood, and have anti-inflammatory activity. For these reasons, in the last few years the production of dietary supplement containing ω3 has increased significantly. In this context, the possibility to obtain ω3 and other high value molecules from alternative sources as fish waste, in accordance with the principles of circular economy, becomes an enormous attractive. In addition, the opportunity of creating new products, with greater health benefits, represents an interesting challenge. The current study was focused on the extraction of ω3 fatty acids and peptides from tuna waste industry, to realize a new dietary supplement. To this purpose, a supercritical fluid extraction (SFE) method was developed to separate, isolate, and enrich the different fractions subsequently used to produce an innovative formulate. The obtained supplement was characterized in terms of fatty acids esterified ester (FAEE) composition by gas chromatography (GC) coupled to both flame ionization detection (FID) and mass spectrometry (MS), and content of heavy metals by inductively coupled plasma–mass spectrometry (ICP-MS).The effects of ω3 supplementation on metabolism and circulating lipid profiles was tested on 12 volunteers and assessed by GC-FID analysis of whole blood collected on paper support (Dried Blood Spot, DBS) at the beginning of the study and after thirty days. The results of plasma fatty acids levels after 30 days showed a significant decrease in the ω6/ω3 ratio, as well as the saturated/polyunsaturated fatty acids (SFA/PUFA) ratio, compared to subjects who took the ω3 ethyl esters unformulated. The novel formulated supplements proved to be extremely interesting and promising products, due to a significant increase in bioavailability, that makes it highly competitive in the current panorama of the nutraceutical industry.

Disturbance of Adaptive Immunity System Was Accompanied by a Decrease in Plasma Short-Chain Fatty Acid for Patients Hospitalized During SARS-CoV-2 Infection After COVID-19 Vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to disorders of immune function and a decrease in the diversity of intestinal flora. We aimed to explore the changes of circulating immune cell subsets and the plasma level of intestinal short-chain fatty acids (SCFAs) in patients with Coronavirus disease 2019 (COVID-19), further understanding the pathogenesis of COVID-19. The study included 83 newly diagnosed COVID-19 patients and 39 non-COVID-19 controls. All have completed a full course of vaccination against SARS-CoV-2. The levels of peripheral lymphocyte subsets and plasma cytokines were detected by flow cytometry. Targeted metabolomics was used to explore the level of SCFAs in plasma. Compared with the non-COVID-19 group, COVID-19 patients showed a decrease in CD19+B cells, CD4+T cells, CD8+T cells, NK cells, CD4+CD8+T cells and CD4-CD8-T cells (all p<0.001) and concomitantly an increase in sIL-2R, IL-6 and IL-10 (all p<0.005). These alterations were more pronounced in those critical patients. In addition, COVID-19 patients had lower levels of propanoic acid (PA), butyric acid (BA), isobutyric acid (IBA) and isohexanoic acid (ICA) (all p<0.01). Among them, the level of ICA is positively correlated with the absolute number of immune cells. Our study suggests the immune cell subsets in COVID-19 patients who had completed vaccination were still severely disturbed and concomitantly lower SCFAs, especially in severe patients with poor prognosis. Lower levels of plasma SCFAs may contribute to lymphopenia in COVID-19. The potential relationship between plasma SCFAs and immune cell reduction provides a new direction for the treatment of COVID-19.