Gut bacteria can convert dietary fatty acids into oxygenated metabolites called oxylipins, which can exert potent lipid mediator functions. The oxylipins derived from C-18 fatty acids are termed octadecanoids and associate with multiple disorders including allergy and metabolic dysregulation. This study presents the synthesis of 17 octadecanoids possessing a hydroxy group (n = 9) or a ketone (n = 8) on the 10- or 13-positions. The products of these two series were prepared for the linoleic acid (LA), α-linolenic acid (ALA) and γ-linolenic acid (GLA) pathways. The synthetic strategies provided 17 putative microbial metabolites of C-18 polyunsaturated fatty acids (PUFAs) with high purities, in 5-13 steps and overall yields from 1.5%-37%. To study the biological formation of these compounds, the parent PUFAs (LA, ALA, GLA) were fed to cultures of Enterococcus faecalis U150 and Lactobacillus acidophilus CCUG 5917, and the octadecanoid products were measured by chiral supercritical fluid chromatography coupled to tandem mass spectrometry (SFC-MS/MS). The compounds containing a hydroxy group on the 10- or 13-position are racemic, forming 9 enantiomeric pairs. Accordingly, of the 17 compounds synthesized, 9 were chiral and 8 were achiral resulting in 26 compounds. An additional 7 commercial bacteria-derived octadecanoids were measured to provide a screen of 33 compounds. Generally, PUFA supplementation resulted in selective formation of the associated octadecanoids. Of the 33 studied compounds, 16 were observed to be formed by E. faecalis and 13 by L. acidophilus. These findings demonstrate the bacteria species-specific formation of octadecanoids, which may have ramifications for associated biological response in the host.

Traditional lipid parameters poorly capture coronary heart disease (CHD) risk in type 2 diabetes mellitus (T2DM). This study compared apolipoprotein (ApoA1, ApoB) and lipoprotein(a) [Lp(a)] profiles between T2DM patients with and without CHD and evaluated their combined predictive value. This retrospective study included 140 T2DM patients, 70 with angiographically confirmed CHD and 70 age- and sex-matched without CHD (defined by the absence of cardiac symptoms, normal electrocardiogram, and normal echocardiogram). Fasting serum levels of traditional lipids, ApoA1, ApoB, and Lp(a) were measured, and the ApoB/ApoA1 ratio was calculated. Multivariate logistic regression and ROC curve analysis identified independent predictors and assessed predictive performance. Traditional lipid parameters showed no significant differences between groups (all p > 0.05). CHD patients had significantly lower ApoA1 (1.33 vs. 1.56 g/L, p < 0.001) and higher ApoB (1.40 vs. 1.21 g/L, p < 0.001), ApoB/ApoA1 ratio (1.05 vs. 0.78, p < 0.001), and Lp(a) (20.65 vs. 14.10 mg/dL, p = 0.009). Multivariate analysis identified smoking, ApoB/ApoA1 ratio, and Lp(a) as independent predictors. The ApoB/ApoA1 ratio yielded an AUC of 0.912. A combined model achieved an AUC of 0.976, with bootstrap internal validation confirming robustness (optimism-corrected AUC = 0.959, 95% CI: 0.921-0.982). The ApoB/ApoA1 ratio and Lp(a) were independently associated with CHD in T2DM patients. The combined model demonstrated excellent predictive performance, maintained after internal validation, though external validation is needed.

Remnant cholesterol and apolipoprotein B (ApoB) are established contributors to coronary artery disease (CAD), but their relationship with very-large VLDL phospholipid composition remains uncertain. We evaluated whether genetically proxied VLDL phospholipid composition is linked to CAD through a connected remnant cholesterol-ApoB axis. Summary-level GWAS data were analyzed using network Mendelian randomization. Primary pairwise analyses used genome-wide significant instruments (P < 5 × 10[-8]) and inverse-variance weighted random-effects models, with weighted median, MR-Egger, MR-PRESSO, Steiger directionality, leave-one-out analyses, multivariable MR (MVMR), and locus-level colocalization as complementary analyses. Higher VLDL phospholipid ratio was associated with higher remnant cholesterol (β = 0.86, 95% CI 0.74-0.99) and higher CAD risk (OR = 1.80, 95% CI 1.54-2.11). Remnant cholesterol was associated with higher ApoB (β = 1.04, 95% CI 1.01-1.08), and ApoB with higher CAD risk (OR = 1.40, 95% CI 1.23-1.59). In MVMR models with adequate conditional instrument strength, VLDL phospholipid ratio remained associated with CAD after adjustment for remnant cholesterol (OR = 1.44, 95% CI 1.07-1.94) or ApoB (OR = 1.60, 95% CI 1.21-2.11), whereas their conditional effects were not independently significant. Remnant cholesterol and ApoB showed near-complete genetic collinearity, limiting reliable separation of their independent effects. colocalization supported shared causal signals at multiple loci. The findings support a genetically connected VLDL-remnant cholesterol-ApoB lipid axis associated with CAD, but do not establish formal serial mediation. VLDL phospholipid composition may capture CAD-relevant biology not fully explained by remnant cholesterol or ApoB alone.

Adequate lipid management is a crucial component in the treatment of chronic coronary syndromes, a group of conditions that also encompasses patients with chronic total coronary occlusions (CTOs). Importantly, atherosclerotic progression may be especially rapid in patients with a CTO, yet it is unknown whether specific lipid thresholds for this population are appropriate or need to be adjusted compared to non-CTO patients. The present review aimed to provide insight into the lipid profiles of CTO patients and their association with clinical outcome compared to non-CTO patients. Furthermore, we investigated the impact of lipid levels on coronary collateral circulation (CCC) development. The available data suggest a tendency towards a more adverse lipid profile in CTO patients compared with non-CTO patients, characterized by elevated TG, Lp(a), and AIP, and reduced HDL levels. While lipid parameters are frequently reported as baseline characteristics, few studies have directly evaluated their prognostic significance. The current evidence supports the hypothesis that a greater atherogenic burden in CTO patients may be associated with worse clinical outcomes and poorer CCC formation, particularly when advanced lipidomic markers or composite indices are considered. If confirmed in larger prospective studies, incorporating a more comprehensive assessment of the lipid profile into the clinical management of CTO patients may improve risk stratification and provide a basis for more personalized lipid-lowering strategies in this high-risk population.

Background and AimsThe relationship between blood lipids and atrial fibrillation (AF) remains unclear. Nuclear magnetic resonance (NMR) spectroscopy enables the profiling of size-defined lipoproteins and their contained lipid components. This study aimed to analyze the genetic causal relationships between lipoproteins, NMR-measured lipids, and AF, providing insights into the prediction and treatment of AF. Methods and Results. Summary-level data on lipoprotein and lipid concentrations measured by NMR were obtained from the UK Biobank. Summary-level data on AF were sourced from the FinnGen project. Mendelian Randomization (MR) analysis using inverse-variance weighting was employed as the primary analytical method. Genetically predicted elevated low-density lipoprotein (LDL) cholesterol, LDL free cholesterol, LDL phospholipids, and LDL total lipids measured by NMR were associated with an increased risk of AF. MR analyses did not identify robust causal associations between lipids contained in high-density lipoproteins (HDL), intermediate-density lipoproteins (IDL), or very-low-density lipoproteins (VLDL) and AF. Among size-defined LDL particles, elevated lipids of large LDL (L-LDL) were strongly associated with increased risk of AF. Hypertension and coronary heart disease mediated these effects. Genetic variation alleles at ABCG5, LDLR, and PCSK9 genes, which reduce lipid levels, were associated with lower risk of AF. Conclusions Increased lipids contained in LDL were associated with elevated risk of AF. L-LDL particles exhibited a clear association with increased AF risk. LDL is identified as a critical lipoprotein for predicting and treating AF.

The joint effects of small dense low-density lipoprotein cholesterol (sd-LDL-C) and ambient PM2.5 exposure on stroke risk remain unclear. This longitudinal cohort study included 6457 stroke-free participants from the China Health and Retirement Longitudinal Study (2011-2020). PM2.5 exposure was estimated from the ChinaHighPM2.5 dataset. Cox regression models assessed hazard ratios (HR) with 95% confidence intervals (CI). K-means trajectory analysis identified sd-LDL-C risk groups. The restricted cubic spline examined the dose-response relationship. During a median 9-year follow-up, 710 stroke cases occurred. Both sd-LDL-C (HR per 1-SD: 1.116, 95% CI: 1.018-1.224) and PM2.5 (HR per 1-SD: 1.321, 95% CI: 1.222-1.428) independently predicted stroke risk. Significant multiplicative interaction was detected (p = 0.037). Combined high sd-LDL-C and high PM2.5 exposure conferred the greatest risk (HR: 1.713, 95% CI: 1.335-2.198) versus double-low exposure. Sustained high sd-LDL-C trajectory increased stroke risk by 36% (HR: 1.361, 95% CI: 1.086-1.706). Cumulative sd-LDL-C (cu-sd-LDL-C) exposure showed dose-dependent associations (Q4 vs. Q1: HR = 1.580, 95% CI: 1.115-2.239). Baseline sd-LDL-C (p = 0.009), annual average PM2.5 (p < 0.001), and cu-sd-LDL-C exposure (p = 0.037) all showed significant nonlinear relationship with incident stroke. sd-LDL-C demonstrated superior predictive ability over conventional LDL-C (AUC: 0.578 vs. 0.534, p < 0.001). Long-term elevated sd-LDL-C and PM2.5 exposure were independently associated with incident stroke risk, and participants with dual-high exposure showed the highest risk. sd-LDL-C outperforms LDL-C in stroke prediction, supporting its integration into risk assessment strategies and the importance of simultaneous lipid and pollution control.

This study investigated the effects of Yinchen lipid-lowering tea (YCLLT) in a rat model of hyperlipidemia. A hyperlipidemic rat model was established using a high-fat diet. After 60 days of low-, middle-, and high-dose YCLLT intragastric administration, body weight, serum total cholesterol (TC), serum triglyceride (TG), high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDL-C), liver TC, liver TG and small intestinal niemann-Pick C1-Like 1 (NPC1L1), apolipoprotein B-48 (ApoB48), and cholesterol acyltransferase 2 (ACAT2) protein expression were measured. The pathological changes of the liver were observed under a light microscope. Compared with the model group, high-dose YCLLT significantly decreased serum TC, TG and LDL-C levels, and elevated high-density lipoprotein cholesterol (HDL-C). Hepatic TC and TG levels were also significantly decreased. Histopathological analysis showed that YCLLT alleviated hepatocellular steatosis and degenerative injury in hyperlipidemic rats. Immunohistochemistry showed that YCLLT significantly downregulated the protein expression of NPC1L1, ApoB48 and ACAT2. Furthermore, serum ApoB48 levels were significantly reduced in all YCLLT-treated groups and positively correlated with serum TG, TC, and LDL-C. In conclusion, these findings demonstrate that YCLLT exerts potent lipid-lowering and liver-protective effects in hyperlipidemic rats, supporting its potential use as a dietary intervention for the management of hyperlipidemia in the future.

Breast cancer remains the most commonly diagnosed malignancy among women worldwide. Although dietary fatty acids have been widely investigated, the relationship between polyunsaturated fatty acids intake and breast cancer risk remains unclear. This study aimed to conduct a systematic review and meta-analysis of cohort studies to elucidate the association between higher dietary intake of omega-3 (ω-3) and omega-6 (ω-6) fatty acids and breast cancer risk. A systematic search of major databases was conducted up to January 2026 to identify eligible cohort studies. Random-effects models were used to pool multivariable-adjusted effect sizes (ESs). Heterogeneity was assessed using the I[2] statistic, and publication bias was evaluated using Begg's and Egger's tests. Sixteen studies on ω-3 and 18 on ω-6 were included. ω-3 intake was not significantly associated with breast cancer risk (ES: 0.97; 95% CI: 0.92-1.02; p = 0.248; I[2] = 10.2%). ω-6 intake also demonstrated no significant overall effect (ES: 1.03; 95% CI: 0.97-1.10; p = 0.384; I[2] = 43.9%). Subgroup analyses revealed regional variability, with American studies showing a significant, small inverse association with ω-6 intake (ES: 0.95; 95% CI: 0.92-0.98; p = 0.002). Sensitivity analyses confirmed the robustness of findings, and funnel plots indicated no substantial publication bias. This meta-analysis found no significant association between higher dietary intake of ω-3 or ω-6 and the risk of breast cancer.

Lipid management after heart transplantation (HT) is complicated by post-transplant dyslipidemia, immunosuppression, statin intolerance, and cardiac allograft vasculopathy (CAV). Proprotein convertase subtilisin/kexin Type 9 (PCSK9) inhibitors lower LDL-C in non-transplant populations, but HT recipients were under-represented in pivotal lipid trials. This updated systematic review and exploratory meta-analysis synthesized full-text evidence of PCSK9 inhibition after adult HT, predominantly with alirocumab or evolocumab. LDL-C lowering was the primary lipid outcome. CAV imaging/physiology, rejection, donor-specific antibodies, immunosuppression stability, and safety were secondary outcomes. PubMed/MEDLINE, Scopus, Cochrane Library, and Google Scholar were searched through June 20, 2026. Sixteen primary studies were included. Two independent randomized trials, EVOLVD and CAVIAR, both conducted during the first post-transplant year, provide the highest-quality evidence. The remaining evidence consists of an EVOLVD physiology/OCT substudy and observational or case-based reports. Ten studies contributed LDL-C effect and variance data. The exploratory random-effects summary estimated an LDL-C reduction of 73.6 mg/dL (95% CI, 58.8-88.4, I[2] = 89.8%). The randomized-trial subgroup showed a smaller but consistent reduction of 41.8 mg/dL (95% CI, 35.9-47.7). Observational estimates were larger but derived from selected, lower-certainty cohorts. Randomized first-year evidence did not show clear improvement in CAV imaging or coronary physiology. PCSK9 inhibition lowers LDL-C after HT and appears tolerable, but CAV modification and graft-outcome benefit remain unproven.

In the present study, black and white chia seed oils were extracted using different novel (supercritical fluid extraction & SFE) and assisted green extraction techniques (ultrasound-assisted solvent extraction & UASE, conventional solvent extraction & CSE), followed by fractionation applying low-temperature crystallization. The oils were fractionated at temperatures ranging from -15°C to -30°C to obtain olein and stearin fractions. The effect of extraction methods and subsequent winterisation on the physicochemical properties, fatty acid profile, antioxidant content, and oxidative stability of the oil fractions was evaluated. Among the tested temperatures, -25°C produced the higher olein yield and iodine value (IV) for both the seed types. Winterisation significantly modified the composition of the olein fraction, increased the refractive index (1.481), iodine value (219.73 g I2/100 g), and the polyunsaturated fatty acids, particularly α-linolenic acid (71.12%), linoleic acid (19.83%), and oleic acid (5.95%) in black chia seed oil. The olein fraction also showed higher concentrations of antioxidants, including total phenolics (43.85 mg GAE/100 g), total tocopherol (63.99 mg/100 g), and total carotenoid (57.76 mg/kg), than the corresponding stearin fraction. Despite a decrease in the induction time of the olein fraction (0.97-0.75 h) corresponding to raw oils, the increased degree of unsaturation outweighed the protective effect of the retained endogenous antioxidants under accelerated oxidation conditions. In conclusion, winterisation effectively concentrated omega-3-rich and antioxidant compounds in the olein fraction, which preferably enhanced its nutritional value and functionality for potential food, cosmetic, and nutraceutical applications.

Despite notable medical advancements, the continuous development of novel cancer therapies remains imperative. In this study, we aimed to evaluate the anticancer activity of liposomes prepared solely from nonnatural myristoylated (saturated C14 chains) or natural cardiolipin to develop a cancer therapies strategy. We calculated IC50 values using a cell proliferation inhibition assay and investigated the underlying mechanisms in cells exhibiting high inhibitory activity using Western blotting and flow cytometry. Calculation of the IC50 revealed that liposomes prepared solely with natural cardiolipin exhibited low toxicity to normal cells (> 100 μM) and showed the strongest toxicity against cancer cells, specifically KMS-12-PE (multiple myeloma cells) (23.5 ± 11.4 μM) among various cancer cells. In contrast, liposomes prepared solely with myristoylated cardiolipin exhibited weak anticancer activity. Furthermore, the mechanism of anticancer activity was evaluated using immunoblotting and flow cytometry. After administration of natural cardiolipin liposomes, CASPASE-3 cleavage was confirmed in KMS-12-PE cells, and the annexin V-positive rate was higher than in the liposome-free control group, suggesting apoptosis induction. These results indicate that natural cardiolipin is nontoxic to normal cells and possesses anticancer activity. This study demonstrated that liposomes formulated with cardiolipin can induce anticancer activity independently. This new finding is considered a foundation for future therapeutic strategies.

In atherosclerosis (AS), the conversion of vascular smooth muscle cells (VSMCs) to a macrophage-like phenotype is a key contributor to plaque instability. Although retinoic acid receptor responder 2 (RARRES2) has been identified as an adipokine implicated in inflammation and metabolism, its role in VSMC phenotypic transformation remains unknown. This study aimed to investigate whether RARRES2 regulates the macrophage-like transformation and dysfunction of VSMCs. In the in vitro AS model, RARRES2 expression was significantly upregulated. Knockdown of RARRES2 inhibited VSMC proliferation and migration, reduced the secretion of inflammatory factors, decreased lipid accumulation, and the number of CD68-positive cells, and suppressed the activation of key proteins in the NF-κB/NLRP3 pathway. In the AS model, RARRES2 expression was found to be significantly upregulated. Knockdown of RARRES2 inhibited the proliferation and migration of VSMCs, reduced the secretion of TNF-α, IL-6, IL-1β, and MMP-2, reduced lipid accumulation, decreased the number of CD68-positive cells (indicating an acquisition of partial macrophage-like features, though further lineage markers are needed to confirm full partial macrophage-like phenotype), and inhibited the activation of key proteins (p-p65, NLRP3, ASC) in the NF-κB/NLRP3 pathway. RARRES2 knockdown suppresses NF-κB/NLRP3 signaling and attenuates macrophage-like transformation, inflammatory responses, and lipid accumulation in VSMCs, suggesting that RARRES2 may represent a potential therapeutic target for AS.

This review explores how the fatty acid (FA) profile of the Amazonian Rhynchophorus palmarum larva (Chontacuro), traditionally eaten for respiratory ailments, might biochemically mitigate viral respiratory infections. During metamorphosis, this insect utilizes its unique FA matrix to survive severe, self-inflicted oxidative and inflammatory tissue stress. The authors hypothesize that when consumed by humans, these insect lipids undergo chylomicron-mediated lymphatic transport. This pathway bypasses initial liver metabolism, delivering unsaturated FAs directly to the pulmonary microvasculature and alveolar macrophages in the lungs. Once there, the FAs are proposed to act via two main mechanisms: One is inflammation resolution, where the ω-3 fraction is hypothesized to be metabolized via the 15-LOX enzyme pathway into Specialized Pro-Resolving Mediators (SPMs) and activate PPAR-α, potentially shifting the immune response from chronic inflammation toward active tissue repair. The other is viral sabotage: The highly unsaturated fats increase cell membrane fluidity, destabilizing the "lipid rafts" that viruses rely on for cellular entry and assembly. While in vitro and in silico models suggest a synergistic "cocktail effect" that primes and then resolves the immune response, the authors note that direct human clinical evidence is currently lacking.

Studies have shown that omega-3 fatty acids may protect against cardiovascular diseases (CVDs) and related metabolic conditions. UK Biobank is a large cohort study that includes data on plasma omega-3 fatty acids at study entry and health outcomes during the follow-up period. The aim of this research is to explore the association between plasma omega-3 fatty acids (total omega-3 fatty acids, docosahexaenoic acid (DHA) and non-DHA omega-3 fatty acids) and cardiometabolic health outcomes by systematically reviewing publications from UK Biobank. Three databases (EMBASE, MEDLINE, CINAHL) were searched in September 2025 using key words. Based on inclusion/exclusion criteria, 16 publications were selected for inclusion (two cross-sectional and 14 longitudinal with a follow-up of 11 to 14 years). Sample size varied between 20,338 and 273,834 across the included studies. Eleven studies reported on CVD outcomes and five on metabolic outcomes. Plasma total omega-3 fatty acids and DHA were inversely associated with risk of coronary heart disease, CVD mortality, heart failure, haemorrhagic stroke and severe fatty liver disease. Plasma total omega-3 fatty acids were also inversely associated with risk of prediabetes and type-2 diabetes, while plasma DHA was also inversely associated with risk of coronary heart disease mortality, ischemic stroke and fatty liver disease. It is concluded that publications based on UK Biobank consistently demonstrate a significant association between higher levels of total omega-3 fatty acids or DHA in plasma and lower likelihood of poor cardiometabolic health outcomes, providing support for guidance for the population to achieve recommended intakes of these fatty acids.

Insufficient physical activity, poor dietary practices, escalating stress levels, and environmental factors are all contributors to the swift rise in obesity, type 2 diabetes mellitus (T2DM), and hypothyroidism worldwide. This study aimed to assess the effects of obesity on lipid profiles, glycemic control, and thyroid function in individuals with T2DM and hypothyroidism. The study included 154 participants: 100 T2DM patients with hypothyroidism and 54 healthy controls. Anthropometric measurements were collected, and biochemical tests, including fasting blood glucose (FBG), hemoglobin A1c (HbA1c), lipid profiles, and thyroid hormone levels; thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were performed. The groups differed significantly (p < 0.05) in age, body mass index (BMI), FBG, HbA1c, TSH, FT3, total cholesterol, and triglycerides. Compared to patients without obesity and controls, diabetic patients with obesity showed higher levels of FBG, HbA1c, cholesterol, triglycerides, and more notable changes in thyroid hormones. Age, FBG, HbA1c, and total cholesterol were found to be significant predictors of obesity by receiver operating characteristic (ROC) curve analysis. The results demonstrate that people suffering from coexisting diabetes, hypothyroidism, and obesity present compromised glycemic control, lipid profile alterations, and thyroid dysfunction. This identifies a metabolic assessment as a primary tool in the management of obese diabetics.