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Background: Asthma is an inflammatory disease. The potential of omega-6 fatty acids to alleviate asthma symptoms through their anti-inflammatory and immunomodulatory effects has been investigated. However, the association of dietary omega-6 fatty acids in childhood and adolescent asthma remains controversial., Objective: The aim of this study was to evaluate the association between dietary intake of omega-6 fatty acids and asthma in children and adolescents in the United States., Methods: We conducted a cross-sectional analysis of 5045 children and adolescents from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2020. Covariates were adjusted, and multivariate logistic regression, restricted cubic splines, threshold effects, and subgroup analyses were used., Results: Of the 5045 participants, 1000 (19.8%) were identified as having asthma. After adjustment for potential confounders, individuals in the second group (T2, 215.3-377.7 mg/kg/day) had an adjusted odds ratio (OR) of 0.70 (95% CI: 0.57-0.86, P = 0.001) for asthma compared with those in the lowest omega-6 fatty acid intake group (T1, < 215.3 mg/kg/day). Similarly, individuals in the third group (T3, > 377.7 mg/kg/day) had an adjusted OR of 0.59 (95% CI: 0.45-0.78, P < 0.001) for asthma. Furthermore, a non-linear (L-shaped) relationship between omega-6 intake and asthma was observed (P = 0.001), with subgroup analyses confirming the stability of the results. In the threshold analysis, a critical turning point was observed at around 384.2 mg/kg/day (OR = 0.996, 95% CI: 0.995-0.998, P < 0.001)., Conclusion: The consumption of omega-6 fatty acids in the diet showed an L-shaped association with asthma among children and adolescents in the United States. A critical turning point was noted at approximately 384.2 mg/kg/day., (© 2024. The Author(s).)

Previous epidemiological studies on the associations between polyunsaturated fatty acids (PUFAs) and cancer incidence have been inconsistent. We investigated the associations of plasma omega-3 and omega-6 PUFAs with the incidence of overall and 19 site-specific cancers in a large prospective cohort. 253,138 eligible UK Biobank participants were included in our study. With a mean follow-up of 12.9 years, 29,838 participants were diagnosed with cancer. The plasma levels of omega-3 and omega-6 PUFAs were expressed as percentages of total fatty acids (omega-3% and omega-6%). In our main models, both omega-6% and omega-3% were inversely associated with overall cancer incidence (HR per SD = 0.98, 95% CI = 0.96-0.99; HR per SD = 0.99, 95% CI = 0.97-1.00; respectively). Of the 19 site-specific cancers available, 14 were associated with omega-6% and five with omega-3%, all indicating inverse associations, with the exception that prostate cancer was positively associated with omega-3% (HR per SD = 1.03, 95% CI = 1.01-1.05). Our population-based cohort study in UK Biobank indicates small inverse associations of plasma omega-6 and omega-3 PUFAs with the incidence of overall and most site-specific cancers, although there are notable exceptions, such as prostate cancer., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

This study investigates the thermal stability of omega fatty acid-enriched vegetable oils, focusing on their behavior under high-temperature conditions commonly encountered during frying. This research aims to evaluate changes in fatty acid composition, particularly the degradation of essential omega-3, -6, and -9 fatty acids, and the formation of harmful compounds such as trans fatty acids (TFAs). Various commercially available vegetable oils labeled as containing omega-3, omega-6, and omega-9, including refined sunflower, high-oleic sunflower, rapeseed, and blends, were analyzed under temperatures from 180 °C to 230 °C for varying durations. The fatty acid profiles were determined using gas chromatography-mass spectrometry (GC-MS). The results indicated a significant degradation of polyunsaturated fatty acids (PUFAs) and an increase in saturated fatty acids (SFAs) and TFAs with prolonged heating. The findings highlight the varying degrees of thermal stability among different oils, with high-oleic sunflower and blended oils exhibiting greater resistance to thermal degradation compared to conventional sunflower oils. This study underscores the importance of selecting oils with favorable fatty acid compositions for high-temperature cooking to minimize adverse health effects associated with degraded oil consumption. Furthermore, it provides insights into optimizing oil blends to enhance thermal stability and maintain nutritional quality, crucial for consumer health and food industry practices.

Linoleic acid (LA), as a part of the wider debate about saturated, omega-6 and omega-3 fatty acids (FAs) and health, continues to be at the center of controversy in the world of fatty acid research. A robust evidence base, however, demonstrates that higher intakes and blood levels of LA are associated with improved cardiometabolic health outcomes. LA lowers total and low-density lipoprotein cholesterol when compared with saturated fatty acids and carbohydrates. Using large prospective datasets, higher blood levels of LA were associated with lower risk of coronary heart disease, stroke and incident type-2 diabetes mellitus compared with lower levels, suggesting that, across the range of typical dietary intakes, higher LA is beneficial. Recent trials of LA-rich oils report favorable outcomes in people with common lipid disorders. However, an LA intake that is too high can impair endogenous synthesis of eicosapentaenoic acid (EPA) from alpha-linolenic acid (ALA), but the threshold at which this becomes clinically relevant is not known. In the absence of a significant intake of EPA and docosahexaenoic acid, an ideal dietary ratio of LA and ALA may be theoretically useful as it provides insight into the likely extent of endogenous EPA synthesis from ALA. Updating dietary reference intakes (DRIs) for LA and ALA is needed; however, there are insufficient data to establish RDAs for these fatty acids. The omega-6 (n-6) to omega-3 (n-3) PUFA ratio is not informative and does not shed meaningful insight about the amount of individual fatty acids in each class needed to confer health benefits., (© 2024. The Author(s).)

Introduction: Metabolic syndrome (MetS) is significantly associated with osteoarthritis (OA), especially in MetS patients with blood glucose abnormalities, such as elevated fasting blood glucose (FG), which may increase OA risk. Dietary modifications, especially the intake of polyunsaturated fatty acids (PUFAs), are regarded as a potential means of preventing MetS and its complications. However, regarding the effects of FG, Omega-3s, and Omega-6s on OA, the research conclusions are conflicting, which is attributed to the complexity of the pathogenesis of OA. Therefore, it is imperative to thoroughly evaluate multiple factors to fully understand their role in OA, which needs further exploration and clarification., Methods: Two-sample univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) were employed to examine the causal effect of metabolic related factors on hip OA (HOA) or knee OA (KOA). The exposure and outcome datasets were obtained from Open GWAS IEU. All cases were independent European ancestry data. Three MR methods were performed to estimate the causal effect: inverse-variance weighting (IVW), weighted median method (WMM), and MR-Egger regression. Additionally, the intercept analysis in MR-Egger regression is used to estimate pleiotropy, and the IVW method and MR-Egger regression are used to test the heterogeneity., Results: The UVMR analysis revealed a causal relationship between FG and HOA. By MVMR analysis, the study discovered a significant link between FG (OR = 0.79, 95%CI: 0.64∼0.99, p = 0.036) and KOA after accounting for body mass index (BMI), age, and sex hormone-binding globulin (SHBG). However, no causal effects of FG on HOA were seen. Omega-3s and Omega-6s did not have a causal influence on HOA or KOA. No significant evidence of pleiotropy was identified., Discussion: The MR investigation showed a protective effect of FG on KOA development but no causal relationship between FG and HOA. No causal effect of Omega-3s and Omega-6s on HOA and KOA was observed. Shared genetic overlaps might also exist between BMI and age, SHBG and PUFAs for OA development. This finding offers a novel insight into the treatment and prevention of KOA from glucose metabolism perspective. The FG cutoff value should be explored in the future, and consideration should be given to demonstrating the study in populations other than Europeans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Leng, Lei, Zhang, Ding and Lo.)

Objectives: The evidence connecting polyunsaturated fatty acids (PUFAs) to biliary problems is still highly contested and speculative despite the fact that biliary diseases are common and PUFAs have long been studied for their potential health benefits. This work used Mendelian randomization (MR) techniques in conjunction with genome-wide association study (GWAS) data to clarify the causal relationships between PUFAs and biliary tract diseases., Methods: We compiled data on PUFAs, including Omega-3 fatty acids, Omega-6 fatty acids, and the ratio of Omega-6 to Omega-3 fatty acids (Omega-6:Omega-3), using GWAS. MR was used to examine biliary tract problems (cholecystitis, cholelithiasis, gallbladder cancer, primary biliary cholangitis, primary sclerosing cholangitis, and disorders of gallbladder, biliary tract and pancreas). Single nucleotide polymorphisms significantly associated with PUFAs were selected as instrumental variables to estimate causal effects on biliary tract diseases. The final results were analyzed using five MR analysis techniques. Inverse variance weighting (IVW) was used as the primary outcome. And IVW was utilized in conjunction with the other MR analysis techniques (MR-Egger, weighted median, simple mode, and weighted mode). Additionally, we evaluated heterogeneity and horizontal multiplicity using the MR-Egger intercept test and Cochrane's Q test, respectively. Finally, to increase the accuracy and precision of the study outcomes, we carried out a number of sensitivity analyses., Results: We found that Omega-3 fatty acids reduced the risk of cholecystitis (OR: 0.851, P = 0.009), cholelithiasis (OR: 0.787, P = 8.76e-5), and disorders of gallbladder, biliary tract and pancreas (OR: 0.842, P = 1.828e-4) but increased the primary biliary cholangitis (OR: 2.220, P = 0.004). There was no significant association between Omega-3 fatty acids and risk of gallbladder cancer (OR: 3.127, P = 0.530) and primary sclerosing cholangitis (OR: 0.919, P = 0.294). Omega-6 fatty acids were associated with a reduced risk of cholecystitis (OR: 0.845, P = 0.040). However, they were not linked to an increased or decreased risk of cholelithiasis (OR: 0.878, P = 0.14), gallbladder cancer (OR: 4.670, P = 0.515), primary sclerosing cholangitis (OR: 0.993, P = 0.962), primary cholestatic biliary cholangitis (OR: 1.404, P = 0.509), or disorders of gallbladder, biliary tract and pancreas. Omega-6:Omega-3 fatty acids were linked to a greater risk of cholecystitis, cholelithiasis, and disorders of gallbladder, biliary tract and pancreas (OR:1.168, P = 0.009, OR:1.191, P = 1.60e-6, and OR:1.160, P = 4.11e-6, respectively). But (OR: 0.315, P = 0.010) was linked to a decreased risk of primary biliary cholangitis. Not linked to risk of primary sclerosing cholangitis (OR: 1.079, P = 0.078) or gallbladder cancer (OR: 0.046, P = 0.402). According to the MR-Egger intercept, our MR examination did not appear to be impacted by any pleiotropy (all P > 0.05). Additionally, sensitivity studies validated the accuracy of the calculated causation., Conclusion: Inconsistent causative relationships between PUFAs and biliary tract diseases were revealed in our investigation. However, Omega-3 fatty acids were found to causally lower the risk of cholecystitis, cholelithiasis, and disorders of gallbladder, biliary tract and pancreas. Omega-3 fatty acids increased the risk of primary biliary cholangitis in a causative way. Omega-3 fatty acids with the risk of gallbladder cancer and primary sclerosing cholangitis did not have any statistically significant relationships. Omega-6 fatty acids were not significantly causally connected with the risk of cholelithiasis, gallbladder cancer, primary sclerosing cholangitis, or disorders of gallbladder, biliary tract and pancreas. However, they did play a causative role in lowering the risk of cholecystitis. Omega-6:Omega-3 fatty acids decreased the risk of primary biliary cholangitis but increased the risk of cholecystitis, gallstone disease, and disorders of gallbladder, biliary tract and pancreas. They had no effect on the risk of gallbladder cancer or primary sclerosing cholangitis. Therefore, additional research should be done to examine the probable processes mediating the link between polyunsaturated fatty acids and the risk of biliary tract diseases., Competing Interests: Declaration of competing interest The authors declare no competing financial interests relevant to this article. All financial and material support for this research has no potential conflicts. This manuscript has not been published and is not under consideration for publication elsewhere., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mutations in the adiponectin receptor 1 gene (AdipoR1) lead to retinitis pigmentosa and are associated with age-related macular degeneration. This study explores the effects of AdipoR1 gene deficiency in mice, revealing a striking decline in ω3 polyunsaturated fatty acids (PUFA), an increase in ω6 fatty acids, and elevated ceramides in the retina. The AdipoR1 deficiency impairs peroxisome proliferator-activated receptor α signaling, which is crucial for FA metabolism, particularly affecting proteins associated with FA transport and oxidation in the retina and retinal pigmented epithelium. Our lipidomic and proteomic analyses indicate changes that could affect membrane composition and viscosity through altered ω3 PUFA transport and synthesis, suggesting a potential influence of AdipoR1 on these properties. Furthermore, we noted a reduction in the Bardet-Biedl syndrome proteins, which are crucial for forming and maintaining photoreceptor outer segments that are PUFA-enriched ciliary structures. Diminution in Bardet-Biedl syndrome-proteins content combined with our electron microscopic observations raises the possibility that AdipoR1 deficiency might impair ciliary function. Treatment with inhibitors of ceramide synthesis led to substantial elevation of ω3 LC-PUFAs, alleviating photoreceptor degeneration and improving retinal function. These results serve as the proof of concept for a ceramide-targeted strategy to treat retinopathies linked to PUFA deficiency, including age-related macular degeneration., Competing Interests: Conflict of interest K. P. is a consultant for Polgenix Inc and serves on the Scientific Advisory Board at Hyperion Eye Ltd. D. S.-K. is a scientific consultant for Visgenx, Inc. All other authors declare that they have no conflict of interests with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality., Methods: We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors., Results: Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all P trend <0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15-38%) higher total mortality, 14% (95% CI, 0-31%) higher cancer mortality, and 31% (95% CI, 10-55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects., Conclusions: Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality., Funding: Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health., Competing Interests: YZ, YS, QY, SS, JB, YS, KY No competing interests declared, (© 2023, Zhang et al.)

Lipid metabolism is closely related to obesity and its complications. Our previous study found that ginsenoside Rk3 (Rk3), a natural bioactive substance derived from ginseng, can effectively alleviate obesity-induced colitis, while its impact on the improvement of the lipid metabolism disorder remains unclear. Here, we demonstrated that Rk3 significantly alleviated inflammation, oxidative stress, and lipid dysregulation in high-fat diet-induced colitis C57BL/6 mice. The potential mechanism by which Rk3 mitigated colon inflammation in the context of obesity may involve the modulation of polyunsaturated fatty acid metabolism with specific attention to n-6 fatty acids, linoleic acid, and arachidonic acid. Rk3 intervention markedly reduced the production of pro-inflammatory factors (PGE2, PGD2, TXB2, HETE, and HODE) by inhibiting cyclooxygenase and lipoxygenase pathways, while enhancing the production of anti-inflammatory factors (EET and diHOME) via cytochrome P450 pathways. Our findings suggest that Rk3 is a potential anti-inflammatory natural drug that can improve obesity-induced intestinal inflammation by regulating lipid metabolism.

Introduction: Unsaturated fatty acids play an essential role in the progression of diabetic nephropathy (DN). However, previous studies were mainly focused on the role of individual unsaturated fatty acid. The serum unsaturated fatty acid patterns (FAPs) in patients with DN remain to be determined., Methods: A total of 135 patients with DN (DN group) and 322 patients with type II diabetes without nephropathy (non-DN group) were included in this study. Clinical data, serum levels of unsaturated fatty acids, and other laboratory indicators were collected. Multivariate logistic regression was applied to identify risk factors for serum unsaturated fatty acid level in both groups. Serum unsaturated fatty acids were subjected to factor analysis to identify distinct FAPs. Multivariable logistic regression was employed to assess the risk of DN associated with different serum FAPs., Results: After adjusting for confounders, three types of unsaturated fatty acid including C20:5 (eicosapentaenoic acid [EPA]), C22:6 (docosahexaenoic acid [DHA]), and C22:5 n -3 (docosapentaenoic acid n -3) were significantly associated with DN in the population. The odds ratios (ORs) (95% confidence interval [CI]) of DN were 0.583 (0.374, 0.908), 0.826 (0.716, 0.954), and 0.513 (0.298, 0.883), respectively. Factor analysis revealed five major FAPs, among which FAP2 (enriched with EPA and DHA) exhibited a significant inverse association with DN. In the multivariate-adjusted model, the OR (95% CI) was 0.678 (0.493, 0.933). Additionally, a combination of DHA and EPA enriched in FAP2 further decreased extracellular matrix production induced by transforming growth factor beta 1 in podocytes and tubular cells., Conclusions: Our findings suggest that FAP2 which is enriched with DHA and EPA is associated with a reduced risk of DN. This highlights the potential of targeting FAP2 for the patients with DN., Competing Interests: Chunsun Dai is Associate Editor of the journal of “Kidney Diseases.” The authors declare that they have no conflicts of interest with the contents of this article., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Findings on the association of dietary intake and tissue biomarkers of linoleic acid (LA) with the risk of prostate cancer are conflicting. Also, no meta-analysis summarized available findings in this regard. Therefore, the current systematic review and dose-response meta-analysis were done to summarize the findings of prospective cohort studies that assessed dietary intake and tissue biomarkers of LA in relation to prostate cancer risk in adults. We conducted a systematic search using online databases, including PubMed, Scopus, and ISI Web of Science, to identify eligible articles published up to January 2023. We included prospective cohort studies that examined the associations of dietary intake and tissue biomarkers of LA with the risk of prostate cancer (total, advanced, and fatal prostate cancer). Summary relative risks (RR) and 95% confidence intervals (CI) were calculated for the highest versus lowest intakes/tissue levels of LA using a fixed-effects model. Also, linear and non-linear dose-response analyses were conducted. In total, 15 prospective cohort studies were included. These studies recruited a total sample size of 511,622 participants with an age range of ≥18 years. During the follow-up periods ranging from 5 to 21 years, 39,993 cases of prostate cancer, 5,929 cases of advanced prostate cancer, and 1,661 cases of fatal prostate cancer were detected. In the meta-analysis, we found that higher tissue levels of LA were associated with a reduced risk of prostate cancer (RR: 0.86, 95% CI: 0.77-0.96) so that in the dose-response analysis, each 5% increase in levels of LA was associated with a 14% lower risk of prostate cancer. Such a significant association was not seen for advanced prostate cancer (RR: 0.86, 95% CI: 0.65-1.13). Also, we found no significant association between dietary intake of LA and risk of total (RR:1.00, 95% CI: 0.97-1.04), advanced (RR: 0.98, 95% CI: 0.90-1.07), and fatal prostate cancer (RR: 0.97, 95% CI: 0.83-1.13). Our findings support the protective association between tissue levels of LA and the risk of prostate cancer in men.

Introduction: Several observational studies have indicated that polyunsaturated fatty acid serum levels (PUFAs) are associated with vascular dementia (VaD), but their causal relationships remain elusive. Therefore, we attempted to evaluate the causal effect of PUFAs on VaD in a two-sample Mendelian randomization (MR) analysis by using summary statistics from aggregated genome-wide association studies., Methods: The inverse-variance weighted (IVW) method was performed as the primary analysis. Sensitivity analyses (MR-Egger regression, weighted median, penalized weighted median, and MR pleiotropy residual sum and outlier methods) were also implemented to estimate the effects of potential violations of MR hypotheses., Results: No causality was found for PUFAs (odds ratio, 1.14; 95% confidence interval, 0.91-1.42; p = 0.25) on VaD in the IVW model. The results were consistent in sensitivity analyses. There was no notable horizontal pleiotropy or heterogeneity., Conclusion: In this two-sample MR analysis, our findings did not support the assumption that PUFAs play causal role in the occurrence or development of VaD., (© 2023 S. Karger AG, Basel.)

Omega-6 fatty acids are the primary polyunsaturated fatty acids in most Western diets, while their role in diabetes remains controversial. Exposure of omega-6 fatty acids to an oxidative environment results in the generation of a highly reactive carbonyl species known as trans, trans-2,4-decadienal (tt-DDE). The timely and efficient detoxification of this metabolite, which has actions comparable to other reactive carbonyl species, such as 4-hydroxynonenal, acrolein, acetaldehyde, and methylglyoxal, is essential for disease prevention. However, the detoxification mechanism for tt-DDE remains elusive. In this study, the enzyme Aldh9a1b is identified as having a key role in the detoxification of tt-DDE. Loss of Aldh9a1b increased tt-DDE levels and resulted in an abnormal retinal vasculature and glucose intolerance in aldh9a1b -/- zebrafish. Transcriptomic and metabolomic analyses revealed that tt-DDE and aldh9a1b deficiency in larval and adult zebrafish induced insulin resistance and impaired glucose homeostasis. Moreover, alterations in hyaloid vasculature is induced by aldh9a1b knockout or by tt-DDE treatment can be rescued by the insulin receptor sensitizers metformin and rosiglitazone. Collectively, these results demonstrated that tt-DDE is the substrate of Aldh9a1b which causes microvascular damage and impaired glucose metabolism through insulin resistance., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a common disease among the elderly, which brings great harm to the health of patients and imposes a huge economic burden on the healthcare system. Research has shown that it is possible to prevent iNPH through nutritional and dietary interventions. Intake of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can reduce the risk of many diseases. In this study, we aimed to explore the association between omega-3/6 PUFAs and iNPH. Methods: We conducted a two-sample Mendelian randomization (MR) study using summary data from publicly available genome-wide association studies (GWAS) to evaluate the potential impact of omega-3 and omega-6 PUFAs on the risk of iNPH in European populations. Inverse variance weighting was used as the main method for MR analysis, with Wald ratio, weighted median, MR-Egger, simple mode, and weighted mode as supplementary methods. In addition, we performed a series of instrument variable strength evaluations and sensitivity analyses to test the reliability of the study results. Finally, we also conducted a linkage disequilibrium score regression (LDSC) analysis to assess the genetic correlation and distinguish between causal associations and shared genetic variants between PUFAs and iNPH. Results: One SD increase in genetically predicted levels of total omega-3 PUFAs (OR: 0.748; 95% CI: 0.597-0.937; p = 0.012; IVW), DHA (OR: 0.709; 95% CI: 0.532-0.945; p = 0.019; IVW), ALA (OR: 0.001; 95% CI: 1.17E-06-0.423; p = 0.026; Wald ratio), and DHA (OR: 0.709; 95% CI: 0.532-0.945; p = 0.019; IVW) were associated with a reduced iNPH risk. LDSC did not reveal any significant genetic correlations. Conclusion: Higher genetically predicted levels of total omega-3 PUFAs, ALA, DHA, and DPA are associated with a reduced risk of iNPH. These findings have important implications for preventing iNPH and future nutritional guidance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Huang, Zhang, Peng and Huang.)

Current Dietary Guidelines for Americans recommend replacing saturated fat (SFA) intake with polyunsaturated fatty acids (PUFAs) and monosaturated fatty acids (MUFAs) but do not specify the type of PUFAs, which consist of two functionally distinct classes: omega-6 (n-6) and omega-3 (n-3) PUFAs. Given that modern Western diets are already rich in n-6 PUFAs and the risk of chronic disease remains high today, we hypothesized that increased intake of n-3 PUFAs, rather than n-6 PUFAs, would be a beneficial intervention against obesity and related liver diseases caused by high-fat diets. To test this hypothesis, we fed C57BL/6J mice with a high-fat diet (HF) for 10 weeks to induce obesity, then divided the obese mice into three groups and continued feeding for another 10 weeks with one of the following three diets: HF, HF+n-6 (substituted half of SFA with n-6 PUFAs), and HF+n-3 (substituted half of SFA with n-3 PUFAs), followed by assessment of body weight, fat mass, insulin sensitivity, hepatic pathology, and lipogenesis. Interestingly, we found that the HF+n-6 group, like the HF group, had a continuous increase in body weight and fat mass, while the HF+n-3 group had a significant decrease in body weight and fat mass, although all groups had the same calorie intake. Accordingly, insulin resistance and fatty liver pathology (steatosis and fat levels) were evident in the HF+n-6 and HF groups but barely seen in the HF+n-3 group. Furthermore, the expression of lipogenesis-related genes in the liver was upregulated in the HF+n-6 group but downregulated in the HF+n-3 group. Our findings demonstrate that n-6 PUFAs and n-3 PUFAs have differential effects on obesity and fatty liver disease and highlight the importance of increasing n-3 PUFAs and reducing n-6 PUFAs (balancing the n-6/n-3 ratio) in clinical interventions and dietary guidelines for the management of obesity and related diseases.

The prior observational research on the impact of polyunsaturated fatty acid (PUFA) supplementation on osteoarthritis (OA) patients had yielded inclusive outcomes. This study utilized the Mendelian randomization (MR) approach to explore potential causal relationships between PUFAs and OA. The MR study was performed using GWAS summary statistics for PUFAs, encompassing omega-3 and omega-6 fatty acids, and for knee OA (KOA) and hip OA (HOA). The primary inverse-variance-weighted (IVW) method and two supplementary MR approaches were used to establish robust causality. Heterogeneity and horizontal pleiotropy were assessed using Cochrane's Q and MR-Egger intercept tests. Additionally, a range of sensitivity analyses were conducted to strengthen the precision and reliability of the results. The IVW method indicated a potential genetic association between omega-3 fatty acids and KOA risk (odd ratio (OR) = 0.94, 95% confidence interval (CI): 0.89-1.00, p = 0.048). No significant correlation was found between omega-3 levels and HOA. Moreover, genetically predicted higher levels of omega-6 fatty acids were associated with a decreased risk of KOA (OR = 0. 93, 95% CI: 0.86-1.00, p = 0.041) and HOA (OR = 0.89, 95% CI: 0.82-0.96; p = 0.003). The MR-Egger intercept evaluation showed no horizontal pleiotropy affecting the MR analysis (all p   >  0.05). Our findings supported the causal relationship between PUFAs and OA susceptibility and offered a novel insight that high omega-6 fatty acids may reduce the risk of KOA and HOA. These results underscore the importance of maintaining optimal levels of PUFAs, particularly omega-6 fatty acids, in individuals with a genetic predisposition to OA. Future research is necessary to validate these findings and elucidate the underlying mechanisms involved.

Background: Increased uptake of essential fatty acids during pregnancy through seafood and supplementation has been shown to positively correlate with gestational age and increased infant birth weight. We aimed to evaluate the effect of maternal dietary intake of essential fatty acids, supplementation on gestational period and infant birth weight., Materials: A literature search with the help of various databases such as PubMed, Google Scholar, Web of Science and Scopus was conducted., Methods: Original research articles and intervention-based studies, which involve an association between dietary intake and supplementation of essential fatty acids during full-term pregnancy on human infant birth outcomes and published from 2011 to 2021, were included., Results: In total, there were 21 intervention-based studies, including full-term pregnant women with or without existing comorbidities, which compared essential fatty acids in the form of dietary sources and supplementation with dietary counseling and with or without placebo. The intervention trials included in this review were conducted in developed and developing countries. Half of the pregnant women who enrolled in the study had comorbidities such as diabetes and hypertension, which might increase their risk of adverse maternal and infant birth outcomes. Most of the studies included in the review have reported a positive association between improvised dietary and supplementation intake of essential fatty acids with increased length of gestation, infant birth weight and other parameters such as head circumference, infant birth length and growth velocity., Conclusion: Positive correlations were found between increased consumption of essential fatty acids in food sources and supplements with improvised infant birth weight and gestational period., (© 2023 Manojna Masina et al., published by Sciendo.)

Natural variations in the 13 C: 12 C ratio (carbon-13 isotopic abundance [δ 13 C]) of the food supply have been used to determine the dietary origin and metabolism of fatty acids, especially in the n-3 PUFA biosynthesis pathway. However, n-6 PUFA metabolism following linoleic acid (LNA) intake remains under investigation. Here, we sought to use natural variations in the δ 13 C signature of dietary oils and fatty fish to analyze n-3 and n-6 PUFA metabolism following dietary changes in LNA and eicosapentaenoic acid (EPA) + DHA in adult humans. Participants with migraine (aged 38.6 ± 2.3 years, 93% female, body mass index of 27.0 ± 1.1 kg/m 2 ) were randomly assigned to one of three dietary groups for 16 weeks: 1) low omega-3, high omega-6 (H6), 2) high omega-3, high omega-6 (H3H6), or 3) high omega-3, low omega-6 (H3). Blood was collected at baseline, 4, 10, and 16 weeks. Plasma PUFA concentrations and δ 13 C were determined. The H6 intervention exhibited increases in plasma LNA δ 13 C signature over time; meanwhile, plasma LNA concentrations were unchanged. No changes in plasma arachidonic acid δ 13 C or concentration were observed. Participants on the H3H6 and H3 interventions demonstrated increases in plasma EPA and DHA concentration over time. Plasma δ 13 C-EPA increased in total lipids of the H3 group and phospholipids of the H3H6 group compared with baseline. Compound-specific isotope analysis supports a tracer-free technique that can track metabolism of dietary fatty acids in humans, provided that the isotopic signature of the dietary source is sufficiently different from plasma δ 13 C., Competing Interests: Conflict of interest R. P. B. has received industrial grants, including those matched by the Canadian government, and/or travel support related to work on brain fatty acid uptake from Arctic Nutrition, Bunge Ltd, DSM, Fonterra, Mead Johnson, and Nestle, Inc. Moreover, R. P. B. is on the executive of the International Society for the Study of Fatty Acids and Lipids and held a meeting on behalf of Fatty Acids and Cell Signaling, both of which rely on corporate sponsorship. R. P. B. has given expert testimony in relation to supplements and the brain and holds the Canada Research Chair in Brain Lipid Metabolism. None of the other authors report a conflict of interest related to research presented in this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: This study in hyperlipidemic rats elucidated the effect of Lactobacillus fermentum MCC2760 on intestinal bile acid (BA) uptake, hepatic BA synthesis, and enterohepatic BA transporters., Main Methods: Diets rich in saturated fatty acids [coconut oil (CO)] and omega-6 fatty acids [sunflower oil (SFO)] at 25 g fat/100 g diet were fed to rats with or without MCC2760 (10 9 cells/kg body weight). After 60 days of feeding, intestinal BA uptake and expression of Asbt, Osta/b mRNA and protein, and hepatic expression of Ntcp, Bsep, Cyp7a1, Fxr, Shp, Lrh-1, and Hnf4a mRNA were measured. Hepatic expression of HMG-CoA reductase protein and its activity and total BAs in serum, liver, and feces were assessed., Key Findings: Hyperlipidaemic groups (HF-CO and HF-SFO) had: 1) increased intestinal BA uptake, Asbt and Osta/b mRNA expression, and ASBT staining 2) increased BA in serum, 3) decreased hepatic expression of Ntcp, Bsep, and Cyp7a1 mRNA, and NTCP staining 4) increased activity of HMG-CoA reductase, 5) increased hepatic expression of Fxr and Shp mRNA, 6) decreased hepatic expression of Lrh-1 and Hnf4a mRNA, and 7) decreased BA in Feces when compared to their respective controls (N-CO and N-SFO) and experimental groups (HF-CO + LF and HF-SFO + LF). Immunostaining revealed increased intestinal Asbt and hepatic Ntcp protein expression in the HF-CO and HF-SFO groups compared to control and experimental groups., Significance: Incorporating probiotics like MCC2760 abrogated hyperlipidemia-induced changes in the intestinal uptake, hepatic synthesis, and enterohepatic transporters of BA in rats. Probiotic MCC2760 can be used to modulate lipid metabolism in high-fat-induced hyperlipidemic conditions., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: 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., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zeng, Lv, Wang, Xue, Zhou, Liu and Yu.)

Breast cancer (BC) is the leading cause of cancer-related deaths in females worldwide and is related to genetic and environmental factors. Dietary components may strongly influence the risk of BC. A possible association was also reported between the fat mass and obesity-associated (FTO) single-nucleotide polymorphisms (SNPs) and BC. This study aimed to investigate the impact of FTO rs9939609 polymorphism on the association between BC and dietary intake. This study was conducted on 180 women with BC as the case group and 360 healthy women as the control group. The dietary intakes were assessed by a valid 168-item food frequency questionnaire (FFQ). The FTO gene was genotyped for rs9939609 polymorphism. After adjusting the confounding variables, there was no significant association between dietary intake and BC in individuals without risk allele. A positive association between dietary intake of omega-6 fatty acids and BC was found only in individuals with risk allele of FTO gene (OR: 1.31, 95% CI: 1.08-1.60, p: 0.006). FTO gene risk allele may influence the effect of diet on breast cancer risk. Further studies are needed to assess the possible effects of the FTO genotype on the association between BC risk and dietary components., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

This double-blind, randomized controlled trial, tested fatty acid (FA) supplementation in children (ages 2- < 6 years) recently diagnosed with Autism Spectrum Disorder (ASD). Participants received daily oral FA supplement containing omega-3 and omega-6 FA, or a placebo for 90 days based on participant weight. Erythrocyte FAs and the cytokines, IL-1β, IL-2, IFNγ, were measured in plasma obtained from serial blood collections. Treatment increased omega-3 and omega-6 FA levels (1.40 mol% for EPA and 1.62 mol% for DHA) and reduced IL-2 levels compared to placebo (- 0.17 pg/mL, 95% CI - 0.31, - 0.02, d = - 0.62). Omega 3-6 treatment was tolerable and adherence was greater than 70%. Future research will assess the effects of Omega 3-6 treatment on ASD symptoms. Registered on 06/08/2018 with ClinicalTrials.gov: NCT03550209., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Oils high in linoleic acid are the main sources of polyunsaturated fatty acids in the human diet. The study attempted to increase the oxidative stability of 11 cold-pressed oils with various linoleic acid percentages by adding phenolic acid derivatives (canolol, guaiacol) at concentrations of 20-100 ppm. The oils were characterized by acid, peroxide and anisidine values, diene, triene, and water contents, fatty acid composition, and bioactive compounds. Their oxidative stability was evaluated before and after the addition of phenolic acid derivatives in the Rancimat test. The results indicate that both additives can be deployed as antioxidants in linoleic acid-rich oils, but canolol elicits a stronger protective effect (over fourfold). 100 ppm of canolol caused a significant increase in the oxidative stability of most oils (31-79%). The guaiacol effectiveness was greater (13-19% increase) at higher concentrations in hemp and poppy oils, but its lower amounts were more relevant for other oils., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Fatty acids have diverse immunomodulatory functions and the potential to be associated with inflammatory responses in sarcoidosis., Methods: The serum levels of multiple long-chain fatty acids (LCFAs) were compared between 63 patients with sarcoidosis and 38 healthy controls. The associations of LCFAs with clinical outcomes of sarcoidosis were also evaluated., Results: The patients with sarcoidosis had significantly lower levels of n-3 poly-unsaturated fatty acids (PUFAs) (p < 0.001) and n-6 PUFAs (p < 0.001) than the healthy controls. However, there were no significant differences in the levels of saturated fatty acids (SFAs) and mono-unsaturated fatty acids (MUFAs) between the two groups. On multivariate logistic analysis, lower levels of n-3 PUFAs, n-6 PUFAs, and n-3/n-6 ratio were predictive of sarcoidosis. Among the patients with sarcoidosis, those with multiple organ involvement had significantly lower levels of n-3 PUFAs and n-3/n-6 ratio than those with single organ involvement. There were no significant differences in the levels of n-6 PUFAs, SFAs, and MUFAs between the patients with multiple and single organ involvement. On multivariate logistic analysis, lower levels of SFAs and n-3/n-6 ratio were predictive of multiple organ involvement. The levels of LCFAs had no significant association with radiographic stage or spontaneous remission., Conclusions: Assessment of LCFA profiles may be useful for the diagnosis of sarcoidosis and evaluation of the disease activity., (© 2022. The Author(s).)

Background: Breast cancer (BC) is the most common cancer of women and the second most common cancer overall globally. Data suggest that the plasma concentration of omega fatty acids (n-3 and n-6) and the impact of the genetic variant are associated with diet-related inflammatory disease, BC. This study was aimed to find an association between genetic variant rs174537 of fatty acid desaturase gene 1(FADS 1) and breast cancer estrogen receptor subtype., Methodology: Hundred and two blood samples from women were quantified for fatty acids by gas chromatography. SNP rs 174537(G > T) showed maximum variability and the strongest genetic determinant in the Genome-wide association study were genotyped using Sanger sequencing., Results: The highest tertile of ALA showed a significantly reduced risk of BC compared to the lowest tertile (OR = 0.2, 95 %CL = 0.1-1.14, P = 0.03). Median values of ALA were higher in GT/TT genotype in ER +ve molecular subtype (P = 0.03) and DPA was higher in GG genotype of ER-ve molecular subtype (P = 0.037). When both the groups were put together the highest tertile of GG tertile showed significantly reduced risk of BC compared with the other lowest tertiles of GG and GT/TT genotypes (OR, 95% CL = 0.45(0.2-0.9)., Conclusion: The high levels of arachidonic acid and low levels of n-3 fatty acids result in a pro-inflammatory milieu and that these pro-inflammatory effects might contribute to BC. We conclude that the individuals with genetically determined lower activity of FADS1(minor allele T) will derive greater advantage from n-3 FAs than those with higher FADS1 activity (G allele) and reduce the BC risk., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Fatty acids (FA) play an important role in health and heart disease risk., Objective: We evaluated relationships of plasma FA levels, especially omega-3 FA, with sex, age, and reported heart disease mortality rates by state in a very large clinical population., Methods: Plasma FA were measured by gas chromatography/mass spectrometry after lipid extraction in 1,169,621 fasting United States subjects grouped according to sex (56.2% female), age (<30, 30-<45, 45-<55, 55-<65, ≥65 years; median age 58.2 years), and state of residence., Results: Plasma FA index values (median±interquartile range), expressed as a percent of total plasma FA, in all subjects were: saturated (14:0+16:0+18:0) 31.4±1.5%; monounsaturated (16:1n7-cis+18:1n9-cis) 21.3±2.2%; trans (16:1n7-trans+18:1n9-trans) 0.45±0.08%; omega-6 (18:2n6-cis+20:3n6+20:4n6) 42.5±3.0%; and omega-3 (20:5n3+22:6n3) 2.57±0.81%. The median eicosapentaenoic acid (EPA, 20:5n3) concentration was 22.1±9.7 μg/mL. Females had significantly (P<0.0001) higher omega-3 FA indices (+6.82%) than males. Subjects ≥65 years of age had a higher omega-3 FA index (+29.68%) and higher EPA levels (+57.05%) than subjects <30 years of age (P<0.00001). EPA concentrations and omega-3 FA indices were below overall median levels in most southern and midwestern states. State-reported heart disease mortality rates were inversely correlated with EPA levels (r=-0.504) and omega-3 FA indices (r=-0.570), and positively correlated with saturated FA indices (r=0.450), all P<0.01., Conclusion: In our large population, females, subjects ≥65 years, and those living in northeastern and western states had higher omega-3 fatty acid levels and lower saturated fatty acid levels than other subjects. Such changes were associated with lower state-wide heart disease death rates., (Copyright © 2022. Published by Elsevier Inc.)

Background: Accumulating evidence has demonstrated the associations of omega-3 or omega-6 polyunsaturated fatty acids (PUFAs) with the disease activity and inflammatory mediators of systemic lupus erythematosus (SLE), but the evidence of causal links of omega-3 or omega-6 PUFAs on the risk for SLE remains inconclusive., Objectives: This study was conducted to evaluate the causal relationships between omega-3/omega-6 PUFAs and SLE by performing the Mendelian randomization (MR) analysis., Methods: Genome-wide significant single-nucleotide polymorphisms (SNPs) were obtained from genome-wide association studies (GWASs) of circulating omega-3/omega-6 levels ( n = up to 13,544) and GWAS meta-analyses of SLE ( n = 14,267), respectively. The bidirectional two-sample MR (TSMR) analysis was conducted to infer the causality., Results: The inverse-variance weighted (IVW) method revealed that genetically determined per SD increase in omega-3 levels were causally associated with an increased risk for SLE (odds ratios [ OR s] = 1.49, 95% CI : 1.07, 2.08, p = 0.021), but no causal effect of omega-6 on the risk SLE was observed (IVW OR = 1.06, 95% CI : 0.72, 1.57, p = 0.759). In addition, there were no significantly causal associations in genetic predisposition to SLE with the changes of omega-3 and omega-6 levels, respectively (IVW beta for omega-3: 0.007, 95% CI : -0.006, 0.022, p = 0.299; IVW beta for omega-6: -0.008, 95% CI : -0.023, 0.006, p = 0.255)., Conclusion: The present study revealed the possible causal role of omega-3 on increasing the risk for SLE, it could be the potential implications for dietary recommendations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Xiang, Xu, He, Hu, Ni and Pan.)

Omega-3 and omega-6 fatty acids are important for neonatal development and health. One mechanism by which omega-3 and omega-6 fatty acids exert their effects is through their metabolism into oxylipins and specialized pro-resolving mediators. However, the influence of oxylipins on fetal growth is not well understood. Therefore, the objective of this study was to identify oxylipins present in maternal and umbilical cord plasma and investigate their relationship with infant growth. Liquid chromatography-tandem mass spectrometry was used to quantify oxylipin levels in plasma collected at the time of delivery. Spearman's correlations highlighted significant correlations between metabolite levels and infant growth. They were then adjusted for maternal obesity (normal body mass index (BMI: ≤30 kg/m 2 ) vs. obese BMI (>30 kg/m 2 ) and smoking status (never vs. current/former smoker) using linear regression modeling. A p -value < 0.05 was considered statistically significant. Our study demonstrated a diverse panel of oxylipins from the lipoxygenase pathway present at the time of delivery. In addition, both omega-3 and omega-6 oxylipins demonstrated potential influences on the birth length and weight percentiles. The oxylipins present during pregnancy may influence fetal growth and development, suggesting potential metabolites to be used as biomarkers for infant outcomes.

Lower concentrations of omega-3 (ω-3) and higher concentrations of omega-6 (ω-6) have been associated with excess weight in adults; however, the information on this relationship in pregnancy remains in its infancy. This study aimed to investigate the association between plasma levels of ω-3 and ω-6 long-chain polyunsaturated fatty acids (PUFAs) and weight gain during the gestational period. This is a prospective cohort study involving 185 pregnant women registered with the prenatal services of a municipality in the northeast of Brazil. The dosage of the serum concentration of fatty acids and the anthropometric measurements were carried out at the baseline, and the women's weight information in the first, second, and third trimesters was collected from their pregnancy cards. Serum fatty acids were determined with the help of gas chromatography. The response variable of this study is the latent variable weight gain in pregnancy, derived from three variables: gestational weight in the first, second, and third trimesters. The main exposure was the plasma concentrations of PUFAs. Structural equation modeling was used for the data analysis. The mean age of the pregnant women was 26.74 years old (SD: 5.96 years). Most of the women had not completed high school (84%) and had a low income (70.86%). It was observed that the ω-3 PUFAs, represented by ALA plasm (alpha-linolenic acid), DHA (docosahexaenoic acid), and the EPA/ALA ratio (eicosapentaenoic acid to alpha-linolenic acid ratio), were negatively associated with the weight gain during pregnancy construct (-0.20, -0.12, and -0.14, respectively). Meanwhile, the PUFAs represented by the ratio between the ω-6 category acids ARA and LA (arachidonic acid and linoleic acid) had a direct and positive association (0.22) with that construct. Excess maternal weight gain was associated with ω-3 and ω-6 plasma levels. The women with the greatest gestational weight gain were the ones that presented the highest ARA/LA ratio (ω-6) and the lowest plasma concentrations of ALA, DHA, and EPA/ALA ratio (ω-3).

Oral mucositis (OM) is a painful condition caused by chemotherapeutic or radiotherapeutic cancer treatments, occurring in patients with different tumour characteristics and locations. OM greatly impacts a patient's quality of life and cancer recovery. Current OM management strategies are not providing sufficient prevention and treatment; new approaches to injury management are needed. Studies on the benefit of omega-3 free fatty acids (FFA) in human health have increased significantly in recent years. FFA properties have been studied extensively, including their potential therapeutic use in inflammatory conditions. However, omega-3 FFA's use as a supplementary treatment for OM has not been clinically tested. Preliminary evidence suggests that utilising FFA to manage OM could be a useful strategy for lesion management, assisting with healthy oral mucosa recovery. This review will describe the incidence, risk factors, biology of OM and the current treatment strategies, leading to a discussion of the utility of omega-3 FFA as a novel therapeutic agent for OM.

Background: Some evidence indicates a potential beneficial effect of omega-6 polyunsaturated fatty acids (n-6 PUFAs) on type 2 diabetes mellitus (T2DM); however, the findings to date remains inconclusive and little is known about whether sex modifies these associations. Therefore, this study aimed to investigate potential sex-specific differences in this associations among Chinese adults. Methods: We conducted a cross-sectional study in an area of Dalian city, China; Chinese men and women who attended the Department of Clinical Nutrition and Metabolism between January and December 2020 were invited to participate in this study. All participants were assessed for basic demographic characteristics, fasting blood glucose, HbA1c, and other serum biomarkers and serum phospholipid FAs. Results: In total, 575 Chinese adult participants (270 men and 305 women) were included in the analysis. Hypertension and dyslipidaemia were more common among men than women, but there were no significant differences between the sexes in fatty acid composition, except for eicosadienoic acid (EA; 20:2n-6) and total monounsaturated fatty acids (MUFA). The age-adjusted OR for having T2DM in the highest quartile of arachidonic acid (20:4n-6) level was 0.47 (95% CI, 0.22, 0.98) in men, and this association remained consistently significant in the fully adjusted multivariate models. In contrast, no significant associations between n-6 PUFAs and T2DM risk were observed in women, regardless of model adjustment. Conclusions: In conclusion, these results demonstrate a notable sex-specific differences in the associations between n-6 PUFAs and T2DM. Higher n-6 PUFA status may be protective against the risk of T2DM in men., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Shen, Li, Bi, Bi, Che, Tian and Liu.)

Background and Aims: The role of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) remains unclear. We investigated the associations of total fat and fatty acids with risk of HCC among US adults in a hospital-based case-control study., Methods: We analyzed data from 641 cases and 1034 controls recruited at MD Anderson Cancer Center during 2001-2018. Cases were new patients with a pathologically or radiologically confirmed diagnosis of HCC; controls were cancer-free spouses of patients with cancers other than gastrointestinal, lung, liver, or head and neck. Cases and controls were frequency-matched by age and sex. Dietary intake was assessed using a validated food frequency questionnaire. Odds ratios (ORs) and corresponding confidence intervals (CIs) were computed using unconditional logistic regression with adjustment for major HCC risk factors, including hepatitis B virus and hepatitis C virus infection., Results: Monounsaturated fatty acid (MUFA) intake was inversely associated with HCC risk (highest vs. lowest tertile: OR, 0.49; 95% CI, 0.33-0.72). Total polyunsaturated fatty acid (PUFA) intake was directly associated with HCC risk (highest vs. lowest tertile: OR, 1.82; 95% CI, 1.23-2.70). Omega-6 PUFA was directly associated with HCC risk (highest vs. lowest tertile: OR 2.29; 95% CI, 1.52-3.44). Long-chain omega-3 PUFA (eicosapentaenoic acid and docosahexaenoic acid) intake was also inversely associated with HCC risk (highest vs. lowest tertile: OR, 0.50; 95% CI, 0.33-0.70). No association was observed for saturated fat and HCC risk., Conclusion: Our findings support a direct association of omega-6 PUFA intake with HCC and an inverse association of MUFA and long-chain omega-3 PUFA intake with HCC., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: We investigated risk of myocardial infarction (MI) associated with the content of linoleic acid (LA) in adipose tissue, a biomarker of long-term dietary intake of LA and a marker of endogenous LA exposure., Methods: Between 1993 and 1997, 57,053 middle-aged subjects were included in the Danish Diet, Cancer and Health cohort. We performed a case-cohort study that included a random sample of the full cohort (n = 3167) and all incident MI cases appearing during 16 years of follow-up (n = 2819). Information on incident MI cases was obtained by linkage with Danish nationwide registries. Adipose tissue biopsies were taken from the buttocks of the participants, and their fatty acid composition was determined using gas chromatography. HRs (hazard ratios) with 95% confidence intervals (CIs) were used to describe the associations between content of LA in adipose tissue and the risk of MI. HRs were calculated using weighted Cox proportional hazards regression with robust variance., Results: After adjustment for established risk factors of MI, adipose tissue content of LA was not associated with the risk of MI in men and women combined (quintiles 5 versus 1, HR, 1.03 (95% CI, 0.85-1.25), P-trend = 0.970) or in men and women separately (quintiles 5 versus 1, HR, 1.05 (95% CI, 0.83-1.33), P-trend = 0.871 and quintiles 5 versus 1, HR, 0.99 (95% CI 0.72-1.37), P-trend = 0.928, respectively). Investigating the association between LA and MI with a shorter, 5- or 10-year duration of follow-up provided similar results., Conclusion: Content of LA in adipose tissue was not associated with the risk of MI., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Oxidative stress and inflammation have been recognized as important contributors to the risk of chronic non-communicable diseases. Polyunsaturated fatty acids (PUFAs) may regulate the antioxidant signaling pathway and modulate inflammatory processes. They also influence hepatic lipid metabolism and physiological responses of other organs, including the heart. Longitudinal prospective cohort studies demonstrate that there is an association between moderate intake of the omega-6 PUFA linoleic acid and lower risk of cardiovascular diseases (CVDs), most likely as a result of lower blood cholesterol concentration. Current evidence suggests that increasing intake of arachidonic acid (up to 1500 mg/day) has no adverse effect on platelet aggregation and blood clotting, immune function and markers of inflammation, but may benefit muscle and cognitive performance. Many studies show that higher intakes of omega-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a lower incidence of chronic diseases characterized by elevated inflammation, including CVDs. This is because of the multiple molecular and cellular actions of EPA and DHA. Intervention trials using EPA + DHA indicate benefit on CVD mortality and a significant inverse linear dose-response relationship has been found between EPA + DHA intake and CVD outcomes. In addition to their antioxidant and anti-inflammatory roles, omega-3 fatty acids are considered to regulate platelet homeostasis and lower risk of thrombosis, which together indicate their potential use in COVID-19 therapy.

Background and Aim: Healthy goat meat is an essential aspect in increasing consumer acceptance for this livestock product. The research aimed to examine the effect of goat meat containing low cholesterol and rich omega-6 fatty acid on the performance and blood lipid status of white rats ( Rattus norvegicus )., Materials and Methods: Thirty 2-month-old male white rats ( R. norvegicus ) weighing 195-230 g were randomly divided into three groups, with each group consisting of 10 rats. Group I was treated with a control feed (T0; BR I concentrate). Group II (T1) was treated with a mixed feed containing 50% control feed and 50% goat meat. Group III (T2) was treated with a mixed feed comprising 50% control feed and 50% goat meat with low cholesterol and rich omega-6 fatty acids. Each treatment was given ad libitum for 30 days. The variables measured were dry matter and organic matter consumption, daily body weight gain, feed conversion, triglyceride levels, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and atherogenic index (AI). The data were analyzed statistically using analysis of variance in a completely randomized design., Results: The total, HDL, and LDL cholesterol levels at T0, T1, and T2 were as follows: 99.97, 35.97, and 50.43 mg/dL (total cholesterol); 108.35, 33.92, and 58.17 mg/dL (HDL cholesterol); and 101.43, 38.09, and 48.65 mg/dL (LDL cholesterol). The highest HDL and the lowest LDL cholesterol levels (p<0.05) were observed in the T2 treatment group, which had the lowest AI (1.69 vs. 1.77 and 2.19)., Conclusion: The consumption of goat with low cholesterol and rich omega-6 fatty acids reduces the total cholesterol and LDL cholesterol, raises the HDL cholesterol levels, and decreases the AI., (Copyright: © Widiyanto, et al.)

Background: Methods to increase the amount of omega-3 (n-3) PUFAs in milk are desirable for neonatal health. The n-3 PUFA, α-linolenic acid (18:3n-3), can be elongated to EPA (20:5n-3) and DHA (22:6n-3). n-6 PUFAs suppress tissue n-3 PUFA incorporation, but the effect of SFAs is not clear., Objectives: In this study, we compared the effects of SFAs and n-6 PUFAs on n-3 PUFA incorporation into milk and tissues of lactating mice and tissues of their offspring., Methods: Female CD-1 mice were bred at 8 wk of age. All experimental diets included 3% flaxseed oil and were begun on day 8 of lactation: low-fat diet (LFD); high-SFA diet (SAT), with an additional 12% saturated oil; or high-linoleic-acid diet (HLA), with 12% high-linoleic-acid oil (% kcal, carbohydrates:fat:protein: LFD, 49:24:27; both SAT and HLA, 35:46:19; n = 5/treatment). After 5 d, pup stomach milk clot FA profiles, tissue FA profiles in dams and pups, and mammary and hepatic expression of lipid metabolism genes in dams were analyzed. Data were analyzed by ANOVA with treatment diet as a fixed effect., Results: Dams in all groups had similar total milk fat concentrations, but both SAT and HLA decreased the concentration of n-3 PUFAs (SAT: -23%; HLA: -31%) compared with LFD, and HLA increased milk n-6 FAs by 347% compared with SAT. SAT pups had n-3 PUFA tissue concentrations similar to LFD, but HLA pups had lower n-3 PUFAs than SAT pups in multiple tissues (liver, -32%; kidney, -29%; heart, -28%; muscle, -18%). Mammary expression of lipid metabolism genes was mostly unchanged, but hepatic expression of elongases and desaturases was decreased with SAT compared with LFD [elongation of very-long-chain fatty acid (Elov)5, -42%; Elov6, -64%; fatty acid desaturase (Fads)1, -33%; Fads2, -44%]., Conclusions: HLA decreased n-3 PUFA concentrations across multiple pup tissues compared with SAT. This suggests that high dietary n-6 PUFAs suppress n-3 PUFA incorporation in neonates., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The dietary recommendation encourages reducing saturated fatty acids (SFA) in diet and replacing them with polyunsaturated fatty acids (PUFAs) n-3 (omega-3) and n-6 (omega-6) to decrease the risk of metabolic disturbances. Consequently, excessive n-6 PUFAs content and high n-6/n-3 ratio are found in Western-type diet. The importance of a dietary n-6/n-3 ratio to prevent chronic diseases is linked with anti-inflammatory functions of linolenic acid (ALA, 18:3n-3) and longer-chain n-3 PUFAs. Thus, this review provides an overview of the role of oxylipins derived from n-3 PUFAs and oxylipins formed from n-6 PUFAs on inflammation. Evidence of PUFAs' role in carcinogenesis was also discussed. In vitro studies, animal cancer models and epidemiological studies demonstrate that these two PUFA groups have different effects on the cell growth, proliferation and progression of neoplastic lesions.

Global beef production must increase in the next decades to meet the demands of a growing population, while promoting sustainable use of limited natural resources. Supplementing beef cattle with omega-6 fatty acids (FAs) is a nutritional approach shown to enhance production efficiency, with research conducted across different environments and sectors of the beef industry. Omega-6 FA from natural feed ingredients such as soybean oil are highly susceptible to ruminal biohydrogenation. Hence, our and other research groups have used soybean oil in the form of Ca soaps (CSSO) to lessen ruminal biohydrogenation, and maximize delivery of omega-6 FA to the duodenum for absorption. In cow-calf systems, omega-6 FA supplementation to beef cows improved pregnancy success by promoting the establishment of early pregnancy. Cows receiving omega-6 FA during late gestation gave birth to calves that were healthier and more efficient in the feedlot, suggesting the potential role of omega-6 FA on developmental programming. Supplementing omega-6 FA to young cattle also elicited programming effects toward improved adipogenesis and carcass quality, and improved calf immunocompetence upon a stress stimulus. Cattle supplemented with omega-6 FA during growing or finishing periods also experienced improved performance and carcass quality. All these research results were generated using cattle of different genetic composition ( Bos taurus and B. indicus influenced), and in different environments (tropical, subtropical, and temperate region). Hence, supplementing omega-6 FA via CSSO is a sustainable approach to enhance the production efficiency of beef industries across different areas of the world.

There are two types of polyunsaturated fatty acids (i.e. fats that contain multiple carbon-carbon double bonds) - omega-6 and omega-3. They are not interconvertible, and they contribute 'double-bonded carbons' to different depths in bilayer membranes, with different effects on membrane processes. This Commentary emphasises the importance of these fats for biological membrane function and examines their evolution and biochemistry. Omega-6 and omega-3 fatty acids are separately essential in the diet of animals, and they pass up the food chain largely from plants, with 'seeds' being a prevalent source of omega-6, and 'leaves' a prevalent source of omega-3. The dietary balance between these fatty acids has a strong influence on membrane composition. Although this aspect of diet has been little investigated outside of the biomedical field, emerging evidence shows it can alter important physiological capacities of animals (e.g. exercise endurance and adiposity), which has implications for activities such as avian migration and hibernation and torpor, as well as significant implications for human health. This Commentary will focus on the separate effects of omega-3 and omega-6 on membrane properties and will emphasise the importance of the balance between these two fatty acids in determining the function of biological membranes; I hope to convince the reader that fats should be considered first and foremost as the basic unit of biological membranes, and secondarily as a means of energy storage., Competing Interests: Competing interests The author declares no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Research Question: Are triglyceride fatty acids in the follicular fluid associated with either follicular fluid phospholipid fatty acids or IVF outcomes and, if so, how are they associated?, Design: In a prospective cross-sectional study, 70 women undergoing intracytoplasmic sperm injection were recruited. Follicular fluid phospholipids and triglycerides were separated by thin-layer chromatography. Fatty acids were measured using gas-liquid chromatography and flame ionization detection system., Results: Significant differences in fatty acid composition were observed between follicular fluid phospholipid and triglyceride fractions. Phospholipid stearic acid and n-3 polyunsaturated fatty acids, particularly alpha-linolenic acid, were negatively associated with the number of mature oocytes and cleaved embryos, whereas arachidonic acid was in direct correlation with cleavage rate per IVF cycle (β = 0.325, P = 0.022). In the case of triglyceride fraction, total monounsaturated fatty acids, oleic acid in particular, displayed significantly positive associations with the number of oocytes (β = 0.261, P = 0.043) and embryos (β = 0.310, P = 0.018). Furthermore, cleavage rate correlated inversely with palmitic acid (β = -0.359, P = 0.007) and directly with pentadecanoic acid (β = 0.378, P = 0.005). Most of these associations, however, were not independent of predictive fatty acids belonging to phospholipid fraction, according to multivariate analysis., Conclusions: Fatty acid compositions of phospholipid and triglyceride fractions from human follicular fluid differentially correlate with IVF cycle parameters., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Gut microbiota is a complex ecosystem seen as an extension of human genome. It represents a major metabolic interface of interaction with food components and xenobiotics in the gastrointestinal (GI) environment. In this context, the advent of modern bacterial genome sequencing technology has enabled the identification of dietary nutrients as key determinants of gut microbial ecosystem able to modulate the host-microbiome symbiotic relationship and its effects on human health. This article provides a literature review on functional and molecular interactions between a specific group of lipids and essential nutrients, e.g., fat-soluble vitamins (FSVs), and the gut microbiota. A two-way relationship appears to emerge from the available literature with important effects on human metabolism, nutrition, GI physiology and immune function. First, FSV directly or indirectly modify the microbial composition involving for example immune system-mediated and/or metabolic mechanisms of bacterial growth or inhibition. Second, the gut microbiota influences at different levels the synthesis, metabolism and transport of FSV including their bioactive metabolites that are either introduced with the diet or released in the gut via entero-hepatic circulation. A better understanding of these interactions, and of their impact on intestinal and metabolic homeostasis, will be pivotal to design new and more efficient strategies of disease prevention and therapy, and personalized nutrition.

Various nutrients have been designated as antioxidants, with a possible effect on diseases like cancer. This is partly due to their effect on prostaglandins, thereby affecting local pathological metabolic acidosis. This paper aims to summarize the culprit pathophysiological mechanisms involved, with a focus on the bone microenvironment. The omega- 6/omega-3 PUFA ratio is particularly investigated for its antioxidative effects, countering these pathways to fight the disease. This feature is looked at concerning its impact on health in general, with a particular focus on malignant bone metastasis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Obesity is a chronic metabolic disease of high complexity and of multifactorial origin. Understanding the effects of nutrition on childhood obesity metabolism remains a challenge. The aim of this study was to determine the fatty acid (FA) profile of red blood cell (RBC) membranes as a comprehensive biomarker of children's obesity metabolism, together with the evaluation of their dietary intake. An observational study was carried out on 209 children (107 healthy controls, 41 who were overweight and 61 with obesity) between 6 and 16 years of age. Mature RBC membrane phospholipids were analyzed for FA composition by gas chromatography-mass spectrometry (GC-MS). Dietary habits were evaluated using validated food frequency questionnaires (FFQ) and the Mediterranean Diet Quality Index for children (KIDMED) test. Compared to children with normal weight, children with obesity showed an inflammatory profile in mature RBC FAs, evidenced by higher levels of ω-6 polyunsaturated FAs (mainly arachidonic acid, p < 0.001). Children who were overweight or obese presented lower levels of monounsaturated FA (MUFA) compared to children with normal weight ( p = 0.001 and p = 0.03, respectively), resulting in an increased saturated fatty acid (SFA)/MUFA ratio. A lower intake of nuts was observed for children with obesity. A comprehensive membrane lipidomic profile approach in children with obesity will contribute to a better understanding of the metabolic differences present in these individuals.

Background: Available data about the effects of circulating polyunsaturated fatty acids (PUFAs) on ischemic stroke (IS) and its main risk factors remains limited and conflicting. Therefore, we conducted Mendelian randomization (MR) to assess whether genetically predicted PUFA affected IS, lipids and blood pressure (BP)., Methods: Genetic instruments associated with IS were derived from ISGC Consortium (n = 29,633), with lipids were derived from GLGC(n = 188,577), with BP were derived from Neale Lab(n = 337,000). The inverse-variance weighted method was the main analysis to estimate the effect of exposure on outcome. Sensitivity analyses included principal components analysis, MR-Egger, weighted median, and weighted mode., Results: Per SD increases in serum α-linolenic acid (ALA) were associated with lower IS risk, with odd ratio (OR) of 0.867(0.782,0.961), arachidonic acid (AA) were associated with higher IS risk (OR: 1.053(1.014,1.094)). Likewise, Per SD increases in ALA were associated with the lower-level low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC) (β:-0.122(- 0.144, - 0.101), - 0.159(- 0.182, - 0.135), - 0.148(- 0.171, - 0.126), respectively), AA were associated with the higher-level of LDL-C, HDL-C and TC (β:0.045(0.034,0.056), 0.059(0.050,0.067), 0.055(0.046,0.063), respectively). Linoleic acid (LA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) had little or no association with IS, lipids or BP at Bonferroni-corrected significance. Different analytic methods supported these findings. The intercept test of MR-Egger implied no pleiotropy., Conclusions: High-level plasma ALA was protective for IS but AA was the opposite. LA, EPA, DHA, and DPA had no effects on IS.

Polyunsaturated fatty acid-derived specialized pro-resolving lipid mediators (SPMs) play an important role in modulating inflammation. The aim of the study was to compare profiles of SPMs, SPM related lipid mediators and SPM receptor gene expression in gingiva of subjects with periodontitis to healthy controls. A total of 28 subjects were included; 13 periodontally healthy and 15 periodontitis before or after non-surgical periodontal therapy. Gingival tissues were collected from two representative posterior teeth prior to and 8 weeks after scaling and root planning; only once in the healthy group. Lipid mediator-SPM metabololipidomics was performed to identify metabolites in gingiva. qRT-PCR was performed to assess relative gene expression (2 -ΔΔCT ) of known SPM receptors. Intergroup comparisons were made using Wilcoxon tests. Thirty-six omega-6 or omega-3 fatty acid-derived lipid mediators and seven receptor genes were identified in gingiva. Profiles of lipid mediators and receptor gene expression were significantly different between the three groups. Levels of six lipid mediators, 5-HETE, 15-HETE, 15(S)-HEPE, 4-HDHA, 7-HDHA, and 17-HDHA in periodontitis before treatment were significantly higher than in periodontitis after treatment. The expression of BLT1 in the healthy group was significantly higher than periodontitis subjects before and after treatment. The expression of GPR18 in periodontitis before treatment was significantly higher than in periodontitis after treatment while the expression of GPR32 in periodontitis before treatment was significantly lower than in periodontitis after treatment. Elevated levels of SPM biosynthetic pathway markers in periodontitis subjects before treatment indicated inflammation induced pro-resolution activity in gingiva, but receptors for these molecules were deficient in periodontitis pre-treatment suggesting that failure of resolution of inflammation contributes to excess, chronic inflammation in periodontitis., (Copyright © 2020 Ferguson, Bokka, Maddipati, Ayilavarapu, Weltman, Zhu, Chen, Zheng, Angelov, Van Dyke and Lee.)

This chapter presents a protocol for assessing the effects dietary seafood consumption on depressive symptoms. We designed a cross-sectional study of 206 participants recruited in two Torres Strait Island communities. Depressive symptoms were assessed using the adapted Patient Health Questionnaire-9 (aPHQ-9), diet was analyzed with a structured questionnaire, omega-3 and omega-6 fatty acid concentrations were measured via a capillary dried blood spot system, and plasma levels of triglycerides and cholesterol were measured by gas-phase chromatography. Finally, we tested the relationship between seafood consumption, blood lipid concentrations, and depression scores using independent samples t-tests and a logistic and quantile regression model.

Introduction The ketogenic diet (KD) is used for drug-resistant epilepsy. However, some patients find only a modest benefit, which may plateau over time. Evidence from several animal and human studies suggests that polyunsaturated fatty acids (PUFAs) may be a beneficial form of treatment for these patients. This retrospective study was conducted to evaluate whether a switch from classic mixed fats KD (MFKD) to a natural polyunsaturated fatty acid KD (PUFA-KD) would improve seizure control. Methods The study evaluated the medical paper record forms of patients who had at least one seizure per week despite the use of MFKD. These patients were started on PUFA-KD and grouped according to the oils preferred. We analyzed the effect on seizure control, tolerability, blood lipids, and adverse effects and whether the type of seizures, age of seizure onset, age at which KD was started, and the ratio of omega 6: omega 3 (n6:n3) fatty acids had any effect on seizure control. Results Data from fifty patients (aged 10 months to 35 years) were analyzed. At the end of six and 12 months on the PUFA-KD, 12% (6) and 16% (8) were seizure-free and 82% (41) and 88% (44) had a >50% reduction in seizures, respectively. The mean seizure control at 12 months was highest in patients with mixed seizures followed by those with generalized seizures and lowest for those with focal seizures. Seizure control at 12 months was inversely correlated to the age of onset of epilepsy and age at initiation of KD. This improvement was independent of the type of PUFAs and the ratio of n6:n3 used. The PUFA-KD was generally well tolerated. Blood lipid levels significantly improved. Conclusion Changing to PUFA-KD improved seizure control in patients who did not respond satisfactorily to MFKD., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2019, Nathan et al.)