Lipids in Health and Disease最新文献

Background: Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality. Insulin resistance and visceral adiposity play pivotal roles in its pathogenesis; however, the prognostic significance of the triglyceride glucose-body roundness index (TyG-BRI) and its interaction with nutritional status remain uncertain.

Methods: A total of 1,015 patients with HFpEF were prospectively enrolled. The TyG-BRI was calculated as the product of the triglyceride-glucose index (TyG index) and the body roundness index (BRI). Cox regression models were used to evaluate its prognostic value for adverse outcomes, with subgroup analyses stratified by nutritional status and mediation analysis assessing the role of exercise tolerance.

Results: During follow-up, 232 (22.9%) all-cause and 158 (15.6%) cardiovascular (CV) deaths occurred. In multivariate Cox regression analysis, patients in the highest TyG-BRI tertile exhibited significantly higher risks of all-cause (hazard ratio [HR] = 2.59, 95% confidence interval [CI]: 1.82-3.71; P for trend < 0.001) and CV mortality (HR = 2.43, 95% CI: 1.59-3.72; P for trend < 0.001) compared with those in the lowest tertile. The prognostic value of the TyG-BRI for all-cause mortality was more prominent among participants with impaired nutritional status (malnourished or at risk of malnutrition) (P for interaction < 0.1). Incorporation of the TyG-BRI into the baseline risk model for all-cause death significantly improved model discrimination (C-statistic = 0.701 vs. 0.626; P < 0.001) and outperformed its individual components (P < 0.05). Mediation analysis further revealed that the six-minute walk distance mediated 14.6% of the association between the TyG-BRI and all-cause mortality.

Conclusions: In patients with HFpEF, the TyG-BRI was independently associated with adverse outcomes, with its prognostic value particularly evident among those with impaired nutritional status. Incorporating the TyG-BRI into the risk model modestly improved prognostic discrimination, and reduced exercise capacity appeared to partly mediate this association.

Fatty acid-binding protein 4 (FABP4), a key member of the fatty acid-binding protein family, is involved primarily in fatty acid transport, metabolic regulation, and inflammatory signaling. In recent years, numerous studies have shown that abnormal FABP4 expression in various tumors influences the metabolism of lipids and its metabolic products in tumors, significantly regulating tumor progression through processes such as oxidative stress, epithelial‒mesenchymal transition, angiogenesis, and the immune microenvironment. This review focuses on the role of FABP4 in tumors and systematically elucidates the specific mechanisms through which FABP4 regulates lipid metabolism and alters the tumor microenvironment. This review also provides an in-depth analysis of the complex network relationship between FABP4-mediated lipid metabolism and the tumor microenvironment and reveals the critical role of FABP4 in tumor occurrence, development, and metastasis, offering a new theoretical basis and potential targets for tumor therapy.

Arachidonic acid (AA), an omega-6 polyunsaturated fatty acid, is abundant in animal-derived food and is widely present in phospholipids of plasma membrane. Recent studies reported that ethanol exposure leads to the activation of prostaglandin signaling via increasing the levels of AA and its metabolites in cardiomyocytes. To test the hypothesis that AA contributes at least in part, to ethanol-induced cardiomyocyte injury, a chronic ethanol feeding model was used, in which male Wistar rats were fed Lieber-Decarli ethanol diet 6.7% (v/v) or isocaloric control diet for 6 weeks. Gas chromatography analysis indicated that ethanol exposure increased the AA content in rat myocardial phospholipids along with increased protein levels of endoplasmic reticulum (ER) stress markers and a decrease in the level of NADH: ubiquinone oxidoreductase subunit B8, a mitochondrial complex I subunit. In addition, an in vitro model was used in which H9c2 cells, a rat cardiomyoblast cell line, were exposed to AA and/or ethanol (ET), and markers of steatosis and endoplasmic reticulum stress, and mitochondrial respiration were assessed. Of note, AA supplementation potentiated ethanol-induced steatosis. H9c2 cells receiving ET + AA showed an increase in the expression of ER stress markers, including glucose-regulated protein 78 and activating transcription factor 4, compared with controls. Interestingly, compared to ET treatment, ET + AA treatment led to a significant decrease in basal respiration and ATP-linked respiration, indicating an impaired mitochondrial respiration in H9c2 cardiomyoblasts. Finally, inhibiting long-chain acyl CoA synthases by Triacsin C attenuated ET + AA treatment-induced steatosis but increased mitochondrial respiration in H9c2 cells. Collectively, these data suggested that AA supplementation promotes ethanol-induced steatosis and endoplasmic reticulum stress with a concomitant impairment in mitochondrial respiration in H9c2 cardiomyoblasts, and Triacsin C treatment inhibits steatosis but enhances mitochondrial respiration possibly via altered fatty acid partitioning between synthetic and oxidative processes.

Background: Schizophrenia (SCZ) patients have high violent and aggressive behavior (VAB) prevalence, causing harm and stigma. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and triglyceride-glucose index (TyG) show promise for psychiatric disorder prediction, but their links to SCZ patients' VAB risk remain understudied.

Methods: A cross-sectional study included 102 hospitalized SCZ patients from May 2023-October 2024, stratified by Broset Violence Checklist (BVC) into low/medium/high VAB risk groups. Positive and Negative Syndrome Scale (PANSS) quantified psychiatric severity; NHHR and TyG were calculated from venous biochemical indices. Analyses included multivariate logistic regression, mediation analysis (PANSS Scores as mediator), 7 machine learning (ML) models with SHAP interpretation, and FDA Adverse Event Reporting System (FAERS) disproportionality analysis.

Results: In fully adjusted models, NHHR and TyG were both negatively associated with VAB risk (NHHR: OR = 0.43, 95%CI:0.20-0.92, p = 0.0285; TyG: OR = 0.29, 95%CI:0.12-0.67, p = 0.0038); further analysis revealed an atypical inverted U-shaped correlation between NHHR and VAB risk, with the inflection point measured at 2.98. Meanwhile, PANSS scores partially mediated the associations between NHHR, TyG and VAB, and TyG had higher mediation proportions (54.2% for BVC scores, 57.8% for VAB risk) than NHHR. In ML-based VAB prediction, LASSO Logistic Regression was the optimal model (Accuracy = 0.8065, highest F1 Score), and SHAP analysis confirmed NHHR and TyG as core predictive features. Additionally, FAERS analysis identified positive metabolic abnormality signals for olanzapine (early-onset adverse events) and quetiapine (late-onset adverse events).

Conclusion: NHHR and TyG are potential VAB risk biomarkers for SCZ patients, with psychiatric severity mediating their effects. ML and FAERS provide clinical prediction and medication monitoring references.

Familial dyslipidemia (FD), particularly familial hypercholesterolemia (FH), is a major contributor to premature cardiovascular disease (CVD), especially in regions with high consanguinity and underutilized genetic screening, such as Egypt. This study aimed to assess clinical, biochemical, and genetic factors that differentiate FD patients with and without CVD, and to develop a composite risk score for individualized stratification. A cross-sectional study was conducted on 60 Egyptian patients aged 15-25 years with genetically confirmed FD, equally divided based on CVD status. All participants underwent detailed clinical assessment, lipid profiling, and targeted next-generation sequencing of LDLR, APOB, and PCSK9 genes. Missense variants were evaluated using SIFT, PolyPhen-2, CADD, and ΔΔG stability scores, and classified according to ACMG criteria. Compared to non-CVD patients, those with CVD had significantly higher triglyceride levels (median: 356.5 vs. 236.5 mg/dL; p < 0.001) and a higher frequency of heterozygous pathogenic LDLR variants (30.0% vs. 3.3%; p = 0.006), while homozygous variants were more common in non-CVD patients (26.7% vs. 0%; p = 0.002). Deleterious missense variants were notably more frequent in the CVD group (56.7% vs. 10.0%; p < 0.001). A 10-variable composite risk score integrating clinical, lipid, and bioinformatic predictors effectively distinguished high- and moderate-risk cases (AUC = 0.742; p = 0.022), with 89.5% sensitivity and 81.8% negative predictive value. The study highlights the importance of combining clinical and genomic data for early risk stratification and introduces a pragmatic tool for identifying high-risk youth in resource-limited, consanguineous populations.

Background: preeclampsia (PE) remains a leading cause of maternal and perinatal morbidity and mortality worldwide. While metabolic and inflammatory factors are increasingly recognized in its pathogenesis, the clinical utility of composite biomarkers remains underexplored. This study aimed to investigate the association between the C-reactive protein-triglyceride-glucose (CRP-TG-glucose) index (CTGI), a novel marker of metabolic-inflammation stress, and the risk of preeclampsia.

Methods: This retrospective cohort study included 11,916 pregnant women, of whom 486 developed preeclampsia. Maternal baseline characteristics were compared between the PE and non-PE groups. Logistic regression analyses were conducted to identify factors associated with PE. The relationship between CTGI and PE risk was further explored using quartile stratification, restricted cubic spline regression, and threshold effect analyses. Subgroup analyses were also performed to assess interaction effects across maternal and obstetric variables.

Results: Women with PE had significantly higher maternal age, body mass index (BMI), in vitro fertilization (IVF) conception, multifetal pregnancies, and elevated CTGI levels compared to non-PE counterparts (all P < .001). Multivariate logistic regression identified CTGI as an independent risk factor for PE (adjusted OR, 1.78; 95% CI, 1.51-2.09; P < .001), alongside BMI, maternal age, IVF, and multifetal gestation. A dose-response relationship was observed across CTGI quartiles, with the highest quartile showing a markedly increased PE risk (adjusted OR, 2.06; 95% CI, 1.52-2.81). Restricted cubic spline models and threshold analysis revealed a nonlinear association with a significant inflection point at CTGI = 2.244. Above this threshold, the risk of PE rose sharply (OR, 3.93; 95% CI, 2.09-7.39; P < .001). Subgroup analyses demonstrated consistent associations across maternal age, BMI, parity, plurality, and IVF status, without significant interaction.

Conclusions: Elevated CTGI in early pregnancy is independently and nonlinearly associated with an increased risk of preeclampsia, particularly above a critical threshold of 2.244. These findings underscore the potential clinical value of CTGI as an early risk stratification biomarker for PE, enabling timely intervention in high-risk pregnancies.

Background: Cardiovascular disease (CVD) remains the leading cause of mortality worldwide. Lipid biomarkers, including direct low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (ApoB), and apolipoprotein A1 (ApoA1), are essential tools for cardiovascular risk assessment. Monitoring patient-derived median values over time may provide insights into population health and analytical performance. This study provides a descriptive analysis of population-level lipid results spanning nearly two decades. While trends in patient medians may support quality assurance, these data do not constitute a validated approach to risk prediction or definitive analytical monitoring due to the absence of outcome and treatment information.

Methods: We retrospectively analyzed routine clinical laboratory data from Uppsala University Hospital, Sweden, covering January 2006-December 2024. A total of 890,948 LDL-C, 867,446 HDL-C, 64,787 ApoB, and 65,500 ApoA1 results were included. Measurements were performed on Abbott Architect systems until 2021, after which assays were transferred to Roche Cobas Pro platforms. Statistical analyses included trend evaluation, variability assessment, and seasonal pattern analysis.

Results: Women had modestly higher LDL-C and HDL-C levels compared to men, while ApoB values were similar between sexes. ApoA1 was notably higher in women. Over the 19-year period, median LDL-C declined from 3.18 to 2.62 mmol/L, consistent with improved lipid management. HDL-C remained stable (1.36-1.45 mmol/L), while ApoB and ApoA1 concentrations showed minimal change. Variability was highest for LDL-C (median CV 6.4%) and lowest for ApoA1 (median CV 2.6%). Seasonal variation was negligible across all analytes. Testing volumes increased substantially for LDL-C and HDL-C, whereas ApoB and ApoA1 requests peaked around 2010 and later declined.

Conclusions: Long-term monitoring of median patient values demonstrates declining LDL-C, stable HDL-C, and consistent ApoB/ApoA1 ratios with minimal seasonal effects. These findings highlight the potential utility of patient medians as supplementary quality indicators and for population-level lipid surveillance.

Objective: To explore if the phospholipid composition in the small airway lining fluid differed between a group of tunnel construction workers exposed to respirable crystalline silica (RCS) and a reference group.

Methods: In total, 19 healthy, non-smoking workers under exposure to RCS and 21 unexposed referents from the same construction site were included. The participants underwent a health examination including lung function measurements and collection of exhaled particles (PEx) using the Particles in exhaled air (PExA) method. Analysis of PEx included determination of lipids. In total, 95 lipid species, primarily phospholipids, were determined. Non-parametric analyses (Wilcoxon rank-sum test and quantile regression), principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used for data analysis.

Results: A difference in mol% of phospholipids between the RCS exposed tunnel construction workers and unexposed referents was observed. On lipid class level there was a higher mol% of sphingomyelin (SM) species among exposed workers compared to referents. Regarding single phospholipid species, higher mol % of phosphatidylcholine (PC) and phosphatidylglycerol (PG) species containing diacyl chains with 18:2 (linoleic acid) and 20:4 (arachidonic acid) fatty acid components were observed in the exposed group. Additionally, lower mol% of saturated PC species were observed among the exposed.

Conclusions: Differences in phospholipid composition in the small airway lining fluid between workers exposed to RCS and a reference group were observed. This indicates a possible impact of RCS exposure on phospholipids in the small airways. However, whether these are linked to health effects is currently not known.