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Purpose of Review: This review aims to examine recent research on the role of specialized pro-resolving mediators (SPMs) in the regulation of gut immunophysiology., Recent Findings: Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gastrointestinal tract, driven by disruptions in the intestinal barrier and an imbalance between the host immune system and gut microbiota. Dietary polyunsaturated fatty acids (PUFAs), especially ω-3 and ω-6, are key regulators of immune responses and help maintain the integrity of the intestinal barrier. These PUFAs serve as precursors to SPMs, lipid mediators that play a critical role in resolving inflammation. SPMs actively reprogram immune cells, promoting the clearance of cellular debris, reducing cytokine production, and restoring tissue homeostasis without suppressing the immune response. Emerging evidence indicates that in the gut, SPMs strengthen intestinal barrier function, modulate immune responses in colitis and colon cancer, and influence gut microbiota composition., Summary: The recent evidence strongly supports the central role of SPMs in maintaining gut health and restoring organ function following inflammatory challenges. This evidence highlights the potential of therapeutic approaches that target these pathways for both the prevention and treatment of gut-related inflammatory conditions., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: S.C.R. Sherratt is an employee of Elucida Research LLC. R.P. Mason receives research funding from Amarin Pharma, Inc, Lexicon Pharma, Inc, Esperion Therapeutics, and Viatris. P. Libby is an unpaid consultant at, or involved in clinical trials for, Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Medimmune, Merck, Moderna, Novo Nordisk, Novartis, Pfizer, and Sanofi-Regeneron. He is a member of the Scientific Advisory Board for Amgen, Caristo Diagnostics, Cartesian Therapeutics, CSL Behring, DalCor Pharmaceuticals, Dewpoint Therapeutics, Elucid Bioimaging, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, Medimmune, Novartis, PlaqueTec, TenSixteen Bio, Soley Therapeutics, and XBiotech, Inc. His laboratory has received research funding in the last 2 years from Novartis, Novo Nordisk and Genentech. He is on the Board of Directors of XBiotech, Inc. He has a financial interest in Xbiotech, a company developing therapeutic human antibodies, in TenSixteen Bio, a company targeting somatic mosaicism and clonal hematopoiesis of indeterminate potential to discover and develop novel therapeutics to treat age-related diseases, and in Soley Therapeutics, a biotechnology company that is combining artificial intelligence with molecular and cellular response detection for discovering and developing new drugs, currently focusing on cancer therapeutics. His interests were reviewed and are managed by Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict-of-interest policies. He Libby receives funding support from the National Heart, Lung, and Blood Institute (1R01HL134892 and 1R01HL163099-01), the RRM Charitable Fund, and the Simard Fund. D.L. Bhatt discloses the following relationships: Advisory Board: Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Stasys; Board of Directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock); consultant: Broadview Ventures, Hims, SFJ, Youngene; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic, Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute; Rutgers University (for the National Institutes of Health–funded MINT trial); honoraria: American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor in chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor; associate editor), K2P (cochair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national coleader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee); other: Clinical Cardiology (deputy editor); patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither he nor Brigham and Women’s Hospital receive any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; royalties: Elsevier (editor, Braunwald’s Heart Disease); site coinvestigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; trustee: American College of Cardiology; unfunded research: FlowCo.

Background and aim: Effects of long-chain omega-3 (LCn3) and omega-6 fatty acids on prevention and treatment of inflammatory bowel diseases (IBD, including Crohn's Disease, CD and ulcerative colitis, UC), and inflammation are unclear. We systematically reviewed long-term effects of omega-3, omega-6 and total polyunsaturated fats (PUFA) on IBD diagnosis, relapse, severity, pharmacotherapy, quality of life and key inflammatory markers. Methods: We searched Medline, Embase, Cochrane CENTRAL, and trials registries, including RCTs in adults with or without IBD comparing higher with lower omega-3, omega-6 and/or total PUFA intake for ≥ 24 weeks that assessed IBD-specific outcomes or inflammatory biomarkers. Results: We included 83 RCTs (41,751 participants), of which 13 recruited participants with IBD. Increasing LCn3 may reduce risk of IBD relapse (RR 0.85, 95% CI 0.72–1.01) and IBD worsening (RR 0.85, 95% CI 0.71–1.03), and reduce erythrocyte sedimentation rate (ESR, SMD − 0.23, 95% CI − 0.44 to − 0.01), but may increase IBD diagnosis risk (RR 1.10, 95% CI 0.63–1.92), and faecal calprotectin, a specific inflammatory marker for IBD (MD 16.1 μg/g, 95% CI − 37.6 to 69.8, all low-quality evidence). Outcomes for alpha-linolenic acid, omega-6 and total PUFA were sparse, but suggested little or no effect where data were available. Conclusion: This is the most comprehensive meta-analysis of RCTs investigating long-term effects of omega-3, omega-6 and total PUFA on IBD and inflammatory markers. Our findings suggest that supplementation with PUFAs has little or no effect on prevention or treatment of IBD and provides little support for modification of long-term inflammatory status. [ABSTRACT FROM AUTHOR]

Background: Observational studies and clinical trials have implicated polyunsaturated fatty acids (PUFAs) in potentially safeguarding against diabetic microvascular complication. Nonetheless, the causal nature of these relationships remains ambiguous due to conflicting findings across studies. This research employs Mendelian randomization (MR) to assess the causal impact of PUFAs on diabetic microvascular complications., Methods: We identified instrumental variables for PUFAs, specifically omega-3 and omega-6 fatty acids, using the UK Biobank data. Outcome data regarding diabetic microvascular complications were sourced from the FinnGen Study. Our analysis covered microvascular outcomes in both type 1 and type 2 diabetes, namely diabetic neuropathy (DN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). An inverse MR analysis was conducted to examine the effect of diabetic microvascular complications on PUFAs. Sensitivity analyses were performed to validate the robustness of the results. Finally, a multivariable MR (MVMR) analysis was conducted to determine whether PUFAs have a direct influence on diabetic microvascular complications., Results: The study indicates that elevated levels of genetically predicted omega-6 fatty acids substantially reduce the risk of DN in type 2 diabetes (odds ratio (OR): 0.62, 95% confidence interval (CI): 0.47-0.82, p = 0.001). A protective effect against DR in type 2 diabetes is also suggested (OR: 0.75, 95% CI: 0.62-0.92, p = 0.005). MVMR analysis confirmed the stability of these results after adjusting for potential confounding factors. No significant effects of omega-6 fatty acids were observed on DKD in type 2 diabetes or on any complications in type 1 diabetes. By contrast, omega-3 fatty acids showed no significant causal links with any of the diabetic microvascular complications assessed., Conclusions: Our MR analysis reveals a causal link between omega-6 fatty acids and certain diabetic microvascular complications in type 2 diabetes, potentially providing novel insights for further mechanistic and clinical investigations into diabetic microvascular complications., 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 Liu, Liu, Gu, Shen, Zhou and Luo.)

Background: Increasing studies have reported a causal relationship between androgenetic alopecia (AGA) and lipid-related metabolites. However, the relationships between HDL-C, LDL-C, Omega-6, and Omega-3 with AGA remain unclear. Some research findings are even contradictory. Therefore, we designed this study to explore this issue., Methods: In this study, we selected seven exposure factors, screened SNPs with significant associations, removed linkage disequilibrium and weak instrumental variables, and conducted bidirectional MR analysis., Results: The study found that omega-6 and LDL-C, especially total cholesterol in medium LDL and total cholesterol in small LDL, are risk factors for the occurrence of androgenetic alopecia., Conclusion: In summary, we found that various lipid-related metabolites have a causal relationship with the occurrence of androgenetic alopecia, providing new insights into the pathogenesis of androgenetic alopecia and offering references for clinical treatment of androgenetic alopecia., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Background: We aimed to explore the association and potential causality between polyunsaturated fatty acids concentrations and the risk of periodontal disease., Materials and Methods: Data were collected from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). Weighted logistic regression analysis and restricted cubic spline (RCS) analysis were used to analyse the associations of the concentrations of omega-3 and omega-6 fatty acids and the omega-6/omega-3 fatty acids ratio with the risk of periodontitis. E-value and propensity score matching (PSM) analyses were used for sensitivity analyses. In addition, two-sample Mendelian randomisation (MR) analyses were performed to assess the potential causal impact of the concentrations of those fatty acids on periodontitis risk., Results: A total of 2462 participants from the NHANES were included. Logistic regression analysis revealed that high omega-3 fatty acids levels were negatively associated with the risk of developing periodontitis (P < 0.05), while the omega-6/omega-3 fatty acids ratio was positively associated with the risk of developing periodontitis (P < 0.05). There was no significant association between omega-6 concentrations and the risk of periodontitis. The findings mentioned above were confirmed by analysis following a 1:1 PSM. Furthermore, MR examination of the two samples indicated no possible causal link between the risk of periodontitis and the concentrations of omega-3 or omega-6 fatty acids or the ratio of omega-6 to omega-3 fatty acids (P > 0.05)., Conclusion: Although omega-3 fatty acids and the omega-6/omega-3 fatty acids ratio were associated with the risk of periodontitis in cross-sectional studies, the MR results did not support a causal relationship between them. Therefore, there is no indication that an increase in the omega-3 fatty acids concentration or a decrease in the omega-6/omega-3 fatty acids ratio may be beneficial for preventing periodontitis., (© 2024. The Author(s).)

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.)

Background & Aims: Leukocyte telomere length (LTL) is a biomarker of aging that may be influenced by dietary factors. Omega-3 fatty acids (n-3 FA) have been suggested to affect LTL. However, research on this effect has been inconclusive. The aim of the study was to test the hypothesis about the positive effect of n-3 FA on LTL., Methods: Fat-1 transgenic mice, which can convert omega-6 fatty acids (n-6 FA) to n-3 FA and have elevated levels of endogenous n-3 FA in their tissues, were used to study the effects of n-3 FA on LTL at different ages. Blood samples from 10-month-old wild-type (WT) mice (n = 10) and fat-1 mice (n = 10) and 3-month-old WT mice (n = 5) and fat-1 mice (n = 5) were used to measure relative and absolute LTL. The levels of proteins critical for telomere maintenance were examined by Western blot analysis., Results: Fat-1 transgenic mice had longer leukocyte telomeres than their WT siblings, suggesting a slower rate of age-related telomere shortening in fat-1 mice. In animals aged 10 months, the LTL was significantly longer in fat-1 than in WT mice (mean ± SEM; relative LTL: WT = 1.00 ± 0.09 vs. fat-1: 1.25 ± 0.05, P = 0.031; absolute LTL: WT = 64.41 ± 6.50 vs. fat-1: 78.53 ± 3.86, P = 0.048). The difference in LTL observed in three-month-old mice was insignificant, however the mean LTL was still longer in fat-1 mice than in the WT mice. Fat-1 mice also had abundant levels of two shelterin proteins: TRF1 (27%, P = 0.028) and TRF2 (47%, P = 0.040) (telomeric repeat binding factor 1 and 2) compared to WT animals., Conclusion: This study, for the first time in a unique animal model free of dietary confounders, has demonstrated that increased levels of n-3 FA in tissues can reduce telomere attrition. The data presented indicate the possibility of using omega-3 fatty acids to reduce accelerated telomere attrition and, consequently, counteract premature aging and reduce the risk of age-related diseases., Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. 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.)

Background & Aims: Inflammation is necessary for a healthy pregnancy. However, unregulated or excessive inflammation during pregnancy is associated with severe maternal and infant morbidities, such as pre-eclampsia, abnormal infant neurodevelopment, or preterm birth. Inflammation is regulated in part by the bioactive metabolites of omega-6 (n-6) and omega-3 (n-3) fatty acids (FAs). N-6 FAs have been shown to promote pro-inflammatory cytokine environments in adults, while n-3 FAs have been shown to contribute to the resolution of inflammation; however, how these metabolites affect maternal and infant inflammation is still uncertain. The objective of this study was to predict the influence of n-6 and n-3 FA metabolites on inflammatory biomarkers in maternal and umbilical cord plasma at the time of delivery., Methods: Inflammatory biomarkers (IL-1β, IL-2, IL-6, IL-8, IL-10, and TNFα) for maternal and umbilical cord plasma samples in 39 maternal-infant dyads were analyzed via multi-analyte bead array. Metabolites of n-6 FAs (arachidonic acid and linoleic acid) and n-3 FAs (eicosapentaenoic acid and docosahexaenoic acid) were assayed via liquid chromatography-mass spectrometry. Linear regression models assessed relationships between maternal and infant inflammatory markers and metabolite plasma concentrations., Results: Increased plasma concentrations of maternal n-6 metabolites were predictive of elevated pro-inflammatory cytokine concentrations in mothers; similarly, higher plasma concentrations of umbilical cord n-6 FA metabolites were predictive of elevated pro-inflammatory cytokine concentrations in infants. Higher plasma concentrations of maternal n-6 FA metabolites were also predictive of elevated pro-inflammatory cytokines in infants, suggesting that maternal n-6 FA status has an intergenerational impact on the inflammatory status of the infant. In contrast, maternal and cord plasma concentrations of n-3 FA metabolites had a mixed effect on inflammatory status in mothers and infants, which may be due to the inadequate maternal dietary intake of n-3 FAs in our study population., Conclusions: Our results reveal that maternal FA status may have an intergenerational impact on the inflammatory status of the infant. Additional research is needed to identify how dietary interventions that modify maternal FA intake prior to or during pregnancy may impact maternal and infant inflammatory status and associated long-term health outcomes., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The maternal fatty acid status plays a key role in influencing pregnancy outcomes. Omega-3 fatty acids are the precursors for E-series (RvE) and D-series resolvins (RvD) and possess anti-inflammatory properties. Pregnancy complications like gestational diabetes mellitus (GDM) are associated with excess maternal inflammation. This study reports the levels of maternal fatty acids across gestation in GDM and non-GDM women, placental fatty acids, resolvins and their association with the maternal fatty acid status. Pregnant women were recruited at 11-14 (V1) weeks and followed at 18-22 (V2) and 26-28 (V3) weeks and at delivery (V4). A total of 209 women who were diagnosed as GDM and 207 non-GDM women were included in this study. Fatty acids were estimated using gas chromatography. The protein levels of resolvins (RvE1, RvE2, RvD1 and RvD2) were measured using ELISA kits. Total PUFAs, eicosapentaenoic acid (EPA), omega-6 fatty acids, linoleic acid (LA) and arachidonic acid (AA) were lower, while saturated fatty acid (SFA) and alpha-linolenic acid (ALA) levels were higher in GDM women at 18-22 weeks. Placental AA was lower ( p < 0.05) in women with GDM. Placental protein levels of RvE1, RvD1 and RvD2 were lower ( p < 0.001 for all) in the GDM group. The maternal delta 5 desaturase index was positively associated, while erythrocyte omega-3 and omega-6 fatty acids were negatively associated with RvE2 at 11-14 weeks. Placental LA and ALA were positively associated with RvD1 and RvD2 ( p < 0.05, for both), respectively. Our findings suggest that the maternal fatty acid status influences pro-resolving mediators which may lead to increased inflammation in GDM.

Objective: The APOA5-1131C allele is related to a worse lipid profile and metabolic response to diet interventions. The present study was designed to investigate the effect of SNP rs662799 on the lipid profile of patients with obesity after a hypocaloric diet with a Mediterranean pattern enriched in ω-6 polyunsaturated fatty acids (PUFA)., Patients and Methods: A population of 362 Caucasian patients with obesity was evaluated. Anthropometric evaluation and serum parameters (lipid profile, insulin, homeostasis model assessment (HOMA-IR), glucose, C reactive protein, and adipokines) were measured at basal time and after 12 weeks. All subjects were genotyped rs662799., Results: The APOA5 variant distribution among the 362 patients with obesity was the following: 87.2% (n=316) (TT) were homozygous for the T allele, 12.2% (n=44) (TC) were heterozygous, and 0.6% (n=2) (CC) were homozygous for the C allele. There were only significant differences in triglyceride levels between genotype groups. After 12 weeks of intervention, the following parameters improved in both genotype groups: adiposity parameters, systolic blood pressure, total cholesterol, LDL cholesterol, leptin, adiponectin, and ratio leptin/adiponectin. Insulin levels (delta: -3.5±0.2 UI/L vs. -1.2±0.6 UI/L; p=0.03), HOMA-IR (delta: -1.6±0.1 units vs. -0.3±0.2 units; p=0.01) and triglyceride levels (delta: -18.8±4.1 mg/dl vs. -3.7 ±3.0 mg/dl; p=0.02) decreased in non-C allele carriers., Conclusions: Our data demonstrate that the minor C allele of the APOA5 gene (rs662799) produces a worse response in triglyceride levels, insulin levels, and HOMA-IR after a ω-6 PUFA enriched hypocaloric diet with Mediterranean pattern.

Over the past three decades, studies have shown that consuming polyunsaturated fatty acids (PUFAs) can enhance animal and human health and welfare through biological, biochemical, pathological, and pharmacological impacts. Furthermore, omega-6 plays key roles in the cardiopulmonary system, including promoting airway relaxation and inhibiting atherosclerosis and hypertension. However, findings from investigations of the effects of omega-6 fatty acids on molecular and cellular activity and discussions on their influence on biomarkers are still unclear. Therefore, the present study aimed to evaluate omega-6 fatty acids, the arachidonic acid (AA), and linoleic acid (LA) effects on C2C12 proliferation, myogenesis morphology, and relative myogenic biomarker expression through the Wnt pathway. C2C12 cells were cultured with and without 25, 50, 100, and 150 µM of LA and AA and then subjected to CCK8, Giemsa staining, RT qPCR, Western blotting, and RNA Sequencing. The CCK8 Assay results showed that 25, 50, 100, and 150 µM LA significantly decreased the viability after 72 h for 25, 50, 100, and 150 µM concentrations. Also, AA supplementation decreased cell viability after 24 h for 150 µM, 48 h for 150 µM, and 72 h for 50, 100, and 150 µM concentrations. Moreover, the LA and AA inhibitory effects noticed through Gimesa staining were morphological changes during myoblast differentiation. Both LA and AA showed inhibiting IGF1 , Cola1 , Col6a2 , Col6a1 , Itga10 , Itga11 , SFRP2 , DAAM2 , and NKD2 effects; however, the depressing effect was higher for AA compared to LA . The previous results were confirmed through Western blotting, which showed that 50 µM LA and AA significantly reduced DAAM2 and SFRP2 protein levels compared to the control. Regarding RNA sequencing results, LA and AA increased the number of differentially expressed (DE) Mt-rRNA and snoRNA; however, the numbers of lncRNA detected decreased compared to the control. Our findings demonstrate that high and moderate LA and AA concentrations reduce primary myoblast proliferation and differentiation. Also, they highlight novel biomarkers and regulatory factors to improve our understanding of how the nutrition of fatty acids can control and modulate the myogenesis and differentiation process through different biomarker families.

Background: We aimed to explore the causal relationship between blood metabolites and the risk of visceral obesity, as measured by visceral adipose tissue (VAT)., Methods: Summary statistics for 486 blood metabolites and total, as well as sex-stratified, MRI-derived VAT measurements, adjusted for body mass index (BMI) and height, were collected from previous genome-wide association studies (GWAS). A two-sample Mendelian Randomization (MR) design was used. Comprehensive evaluation was further conducted, including sensitivity analysis, linkage disequilibrium score (LDSC) regression, Steiger test, and metabolic pathway analysis., Results: After multiple testing correction, arachidonate (20:4n6) has been implicated in VAT accumulation (β = 0.35, 95%CI:0.18-0.52, P < 0.001; FDR = 0.025). Additionally, several blood metabolites were identified as potentially having causal relationship (FDR < 0.10). Among them, lysine (β = 0.67, 95%CI: 0.28-1.06, P < 0.001; FDR = 0.074), proline (β = 0.30, 95%CI:0.13-0.48, P < 0.001; FDR = 0.082), valerate (β = 0.50, 95%CI:0.23-0.78, P < 0.001, FDR = 0.091) are associated with an increased risk of VAT accumulation. On the other hand, glycine (β=-0.21, 95%CI: -0.33-0.09), P < 0.001, FDR = 0.076) have a protective effect against VAT accumulation. Most blood metabolites showed consistent trends between different sexes. Multivariable MR analysis demonstrated the effect of genetically predicted arachidonate (20:4n6) and proline on VAT remained after accounting for BMI and glycated hemoglobin (HbA1c). There is no evidence of heterogeneity, pleiotropy, and reverse causality., Conclusion: Our MR findings suggest that these metabolites may serve as biomarkers, as well as for future mechanistic exploration and drug target selection of visceral obesity., (© 2024. The Author(s).)

Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is essential for fetal growth and development. A maternal high LA (HLA) diet alters cardiovascular development in adolescent rats and hepatic function in adult rats in a sex-specific manner. We investigated the effects of an HLA diet on adolescent offspring hepatic lipids and hepatic lipid metabolism gene expression, and the ability of the postnatal diet to alter these effects. Female Wistar Kyoto rats were fed low LA (LLA; 1.44% energy from LA) or high LA (HLA; 6.21% energy from LA) diets during pregnancy and gestation/lactation. Offspring, weaned at postnatal day (PN) 25, were fed LLA or HLA and euthanised at PN40 ( n = 6-8). Maternal HLA increased circulating uric acid, decreased hepatic cholesterol and increased hepatic Pparg in males, whereas only hepatic Srebf1 and Hmgcr increased in females. Postnatal (post-weaning) HLA decreased liver weight (% body weight) and increased hepatic Hmgcr in males, and decreased hepatic triglycerides in females. Maternal and postnatal HLA had an interaction effect on Lpl , Cpt1a and Pparg in females. These findings suggest that an HLA diet both during and after pregnancy should be avoided to improve offspring disease risk.

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/aim: The prevalence of cognitive impairment (CI) is high in hemodialysis patients. In this study, the relationship between CI and serum carnitine, plasma omega-3, omega-6 and omega-3/omega-6 fatty acid ratio was evaluated in hemodialysis patients., Materials and Methods: Sixty two patients [male: 40 (64.5%), mean age 51±13 years] were included in this cross-sectional study. Serum total and free-carnitine levels were determined by ELISA. Plasma omega-3 [eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)] and omega-6 [arachidonic acid (AA), dihomo gamma linoleic acid (DGLA)] levels were measured using LC-ESI-MS/MS. According to the Montreal Cognitive Assessment (MoCA) scores, ≤24 points were considered as CI. MoCA score ≤24 and >24 were determined as Group 1 and Group 2, respectively., Results: Group 1 had significantly higher AA+DGLA/EPA+DHA ratios and lower free-carnitine, DHA and EPA+DHA levels compared to Group 2 (P=0.008, P=0.040, P=0.032, P=0.032, respectively). Group 1 had a statistically lower education level (P<0.05). Negative correlation was found between MoCA scores and AA+DGLA/EPA+DHA ratios (r s =-0.284, P=0.026). Free-carnitine levels were positively correlated with EPA and EPA+DHA levels (r s =0.278, P=0.030 and r s =0.271, P=0.034, respectively), and negative correlated with AA+DGLA/EPA+DHA ratios (r s =-0.414, P=0.001). In multivariate logistic regression analysis, MoCA scores was associated with AA+DGLA/EPA+DHA ratio (P=0.009) and education level (P<0.001)., Conclusion: It was determined that high AA+DGLA/EPA+DHA ratio and low education level could be independent risk factors of the CI. It has been shown that free-carnitine level can have positive effects on plasma EPA+DHA and AA+DGLA distributions. Low omega-3 fatty acid levels may be associated with CI in hemodialysis patients, and low carnitine level may contribute partially to this process. In addition, cognitive education programs may have an effect on preventing CI in hemodialysis patients with low education levels., (Copyright © 2022 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To assess the associations of omega-3 and omega-6 fatty acids consumption, and the ratio between the two, with self-reported doctor told Systemic Lupus Erythematosus (SLE) diagnosis. Further, to assess whether initiation of omega-3 supplements intake was related to time/year of SLE diagnosis., Methods: Data from 42,398 women in the Adventist Health Study-2 cohort were used for this cross-sectional study. Unconditional logistic regression modeling was used for all analyses with the following candidate covariates: age, race, education, smoking, and body mass index (BMI)., Results: Compared to non-cases, participants with a diagnosis of SLE reported higher intakes of total omega-3 fatty acids and about the same intakes of omega-6 fatty acids. Overall, they had higher ratios of omega-3 to omega-6 fatty acids. When assessing odds ratios of SLE diagnosis by quartiles of omega-3 to omega-6 and DHA+EPA to omega-6, there was a positive significant trend (p trend = 0.005). Additionally, among those reporting intake of fish oil, 87% had initiated fish oil consumption around the time of SLE diagnosis. SLE was more likely to occur among Black women compared to White women, among ever smokers compared to never smokers, among overweight women compared to women with normal/underweight, and among women 50-59 years compared to those 30-49 year old. When a smaller 6 year follow-up study identified 64 incident SLE cases and assessed their omega-3 intake at baseline (6 years earlier and before the SLE diagnosis) their intake of omega-3 and fish oil was no different than among non-cases., Conclusion: We observed a significant positive association between the ratio of omega-3 to omega-6 fatty acids consumption and prevalence of SLE. Among those with prevalent SLE, their year of starting supplementation of omega-3 and fish oil was closely linked to year of SLE diagnosis. Further, baseline intake of omega-3 fatty acids was not increased among 64 incident SLE cases identified during 6 years of follow-up. Our surprising finding can best be explained by reverse causation. This could be an example of how public health information is assimilated and acted upon by a health conscious public., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background & Aims: Infertility has been increasing among Iranian couples. Some epidemiological studies have reported a relationship between infertility and lifestyle patterns, including dietary habits. Our objective was to evaluate the relationship between sperm parameters and the intake of dietary fatty acids and minerals among Iranian infertile men., Methods: This cross-sectional was performed on 400 newly diagnosed infertile men at Yazd Reproductive Sciences Institute from July to December 2019. Men whose infertility was confirmed by an andrologist based on the World Health Organization (WHO) criteria were selected. They delivered a semen sample and answered a 168-item semi-quantitative food frequency questionnaire. All data were analyzed using SPSS and STATA software. A p-value of less than 0.5 was considered significant., Results: In the adjusted model, a significant negative association between sperm motility and the 3rd quartile (Q) of poly-unsaturated fatty acids compared to the 1st quartile) P = 0.02). Also, in the adjusted model, total mobility was significantly increased in the second, third and last quartiles of omega-3 fatty acids compared to the first quartile (P < 0.001, P = 0.02, P < 0.001, respectively). Furthermore, omega-6 fatty acid intake in the last quartile were positively associated with sperm motility (P = 0.01). Moreover, there was a significant association between omega-3 fatty acid intake in the second, third, and last quartiles and sperm normal morphology (P = 0.003, P = 0.018, and P = 0.005, respectively) compared with the first quartile. Further, we observed a significant association between omega-6 fatty acid intake and sperm normal morphology in the last quartile compared with the reference quartile (P = 0.04). Also, the findings showed a significant negative association between the second quartile of sodium and calcium intake and sperm volume compared with the first quartile (P = 0.04, for both) in the adjusted model., Conclusions: We concluded that dietary polyunsaturated fatty acid, sodium, and calcium intake are related to sperm morphology, volume, and total motility in Iranian infertile men. However, more research is needed to confirm these relationships and provide evidence to exert these findings into clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Ltd.)

The study explored the potential protective influence of cannabidiol (CBD) on myocardial inflammation state, with a special focus on arachidonic acid (AA), and oxidative balance in lipid overload conditions. The 7-week experiment was conducted on male Wistar rats receiving standard or high-fat diet (HFD) with intraperitoneal CBD injections for the last 14 days. The n-3 and n-6 polyunsaturated fatty acids (PUFAs) activities and AA concentration in selected fractions were evaluated by gas-liquid chromatography (GLC). The expression of proteins was determined by Western blot and the concentration of different parameters by ELISA, colorimetric, or multiplex assay kits. Our results revealed that CBD increased n-3 PUFAs activity in phospholipid and triacylglycerol fractions, and decreased AA content in the HFD group, especially in the phospholipid pool. Simultaneously, CBD decreased the expression of nuclear factor kappa B, cyclooxygenase-1, and - 2, resulting in the reduction of prostaglandin E2 and the increment of prostaglandin I2. CBD appears to be relatively safe for the treatment of obesity-induced heart disease, as it has anti-inflammatory and partially antioxidative properties., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background & Aims: Fatty acids (FAs) of the omega-3 and omega-6 family are considered essential, and adequate intake seems to be associated with lower risk of developing chronic non-communicable diseases. The objective was to evaluate the association of omega-3 and omega-6 FAs dietary intake with the prevalence of MS and its components waist circumference (WC), blood pressure (BP), fasting blood glucose, triglycerides and High Density Lipoprotein - cholesterol (HDL-c) in Brazilian adolescents aged 12-17 years., Methods: This is a school-based cross-sectional investigation, using data from the Study of Cardiovascular Risks in Adolescents (ERICA), carried out between 2013 and 2014. The following variables were collected and assessed: 1) sociodemographic (sex, age, type of school, school location whether urban or rural and region of the country); 2) food consumption was measured through a 24-h Food Recall (24 hR), and a second 24 hR was applied to 7% of the total sample; 3) anthropometrics (weight, height, WC), BP and biochemical (glycemia, triglycerides and HDL-c) were also assessed. Logistic regression analysis was performed according to gender and age group., Results: A total of 36,751 adolescents participated in the study. The intake of omega-3 FAs in the total population was 1.71 g/day and of omega-6 FAs, 13.56 g/day, with an omega-6/omega-3 ratio of 7.93:1. It was found that higher intake of omega-3 FAs was associated with an 53% lower chance of low HDL-c. For omega-6 FAs, no significant results were found., Conclusions: The findings indicated an association between omega-3 FAs and HDL-c. More studies are needed to elucidate the effects of omega-6 FAs., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

PURPOSE: To evaluate the antioxidant and antiperoxidative effects of oil mixes of high ratio Omega-9:Omega-6 and low ratio Omega-6:Omega-3 in the third day after tooth extraction in rats. METHODS: Thirty-two male Wistar rats (270-310g) were randomly distributed in two groups: Control (n=24) and Test (n=8). Control group was divided into three subgroups (n=8): G1: Sham-Saline; G2: Saline; G3: Isolipid. G1 and G2 animals received NaCl 0.9% while G3 rats were treated with an isolipid mixture (alpha-linolenic acid - ALA) containing -6/-3 oils (8:1 ratio) and-9/-6 (0.4:1 ratio). Test group animals (G4) received oily mixtures (alpha-linolenic acid - ALA, docosahexaenoic acid - DHA, eicosapentaenoic acid - EPA) of -6/-3 (1.4:1 ratio) and -9/-6 (3.4:1 ratio). Saline and oils were administered by gavage during four days before and three days after first mandibular molar extraction. Following, samples (arterial blood and alveolar mucosa) were collected for glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) assays. RESULTS: Oil mixes induced a significant decrease in GSH and TBARS tissue and plasma concentrations in the third day post-surgery. CONCLUSION: Gavage administration of oil mixes of high ratio Omega-9:Omega-6 and low ratio Omega-6:Omega-3 after molar extraction in rats induces a significant decrease in lipid peroxidation.