Lipids in Health and Disease最新文献

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a demyelinating condition in the central nervous system whose relapses cause severe disability progression. Although conventional blood lipid markers are linked to disease course and outcomes, the predictive value of emerging lipid indicators, such as remnant cholesterol (RC) and lipid ratios, for NMOSD relapse remains unclear.

Methods: The single-centre retrospective study enrolled a total of 245 patients diagnosed with NMOSD, based on the availability of clinical and laboratory data. To evaluate RC and lipid ratios in predicting NMOSD relapse, multivariate Cox proportional hazards models and restricted cubic spline evaluations were applied. Predictive performance was assessed using the concordance index (C-index), continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Subgroup evaluations examined the stability of the observed RC-relapse connection across diverse patient strata. Cumulative hazard function curves illustrated the clinical relevance of the RC inflection point. Additionally, mediation analyses tested whether inflammatory markers mediated the RC effect on relapse.

Results: Among 245 NMOSD patients, 55.10% of the patients relapsed during follow-up. RC, non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio, total cholesterol and low-density lipoprotein cholesterol levels emerged as independent determinants of relapse across both continuous and categorical Cox models, after adjusting for demographic, clinical and therapy-associated factors. An "S"-shaped nonlinear relationship was observed between RC values and relapse risk, with a turning point at 0.46 mmol/L: protective below, risk factor above. Performance metrics (C-index, NRI, IDI) indicated that RC significantly improved relapse prediction. The RC-relapse association persisted across subgroups, with the inflection point effectively distinguishing relapsing patients in the anti-aquaporin 4-immunoglobulin G seropositive and monoclonal antibody treatment group. Mediation analysis revealed increased neutrophil ratio and decreased lymphocyte ratio partially mediated RC's effect on relapse.

Conclusions: RC was identified as the most robust lipid metabolism indicator for predicting NMOSD relapse, displaying an inflection at 0.46 mmol/L. Neutrophil ratio and lymphocyte ratio may partially mediate the relationship between elevated RC and relapse. These findings aid timely recognition of patients at elevated risk and provision of individualised therapeutic interventions to reduce disability and improve long-term outcomes in this debilitating disease.

Background: Circulating PCSK9 concentrations have been linked to various metabolic disorders, with evidence suggesting sex-specific differences-stronger associations in women and inconsistent findings in men.

Methods: This study enrolled 7,950 participants from the Taiwan Biobank. Associations of PCSK9 concentration with insulin resistance (IR), metabolic syndrome (MetS), diabetes mellitus (DM), and long-term outcomes were analyzed. Anthropometric, biochemical, and hematologic parameters were examined in a subgroup of 6,478 participants, and 4,185 participants underwent abdominal sonography for the assessment of metabolic dysfunction-associated steatotic liver disease (MASLD).

Results: Increasing PCSK9 concentrations and quartiles were significantly associated with older age, female sex, adverse cardiometabolic traits, and several hematological parameters. Higher hematocrit count, higher triglyceride, low-density lipoprotein cholesterol, fasting plasma glucose, and gamma-glutamyl transferase concentrations, and lower total bilirubin concentrations were independently associated with high PCSK9 concentration, with these associations being more pronounced among female participants. Higher platelet count was independently associated with high PCSK9 concentration only in female participants. Odds ratios for IR, MetS, DM, and MASLD increased progressively across PCSK9 quartiles, with stronger associations in women. Kaplan-Meier survival and Cox regression analyses indicated associations of high PCSK9 concentration with higher all-cause, non-cardiovascular, and cancer mortalities, especially in women.

Conclusion: High circulating PCSK9 concentration is independently associated with increased risks of IR, MetS, DM, MASLD, and all-cause and cancer mortality, indicating poor metabolic profiles and outcomes in the Taiwanese population. These associations are stronger in women, highlighting the importance of sex-specific risk evaluation in metabolic diseases and long-term outcomes.

Background: The triglyceride-glucose (TyG) index is an important determinant influencing the incidence of cardiometabolic multimorbidity (CMM). However, it remains unclear whether combining the TyG index with novel obesity indices (CVAI/BRI/ABSI/WWI) can improve the risk stratification of CMM. This study aimed to systematically compare the incremental risk assessment and predictive value of the TyG index, TyG-traditional obesity indices (TyG-WC/TyG-WHtR/TyG-BMI), and TyG-novel obesity indices (TyG-CVAI/TyG-BRI/TyG-ABSI/TyG-WWI) for CMM.

Methods: Trajectory changes and cumulative exposure of TyG-related parameters were quantified using repeated measurements from the CHARLS cohort (n = 3,885). The study endpoint CMM was defined as a comorbid condition encompassing two or more cardiometabolic diseases, namely diabetes, stroke and heart diseases. A multi-model analytical strategy was employed to evaluate the associations between TyG-related parameters and CMM, as well as the contribution of their components. The net reclassification index and integrated discrimination improvement were employed to evaluate the improvement in predictive performance of these indices.

Results: Over a median follow-up period of 8 years, we identified a linear positive association between TyG-related parameters and CMM, with the cumulative effects of glucose and obesity emerging as the key drivers. Compared with the baseline TyG index, the incremental risk assessment value for CMM improved by 10%-17% (baseline) and 12%-20% (cumulative exposure) for TyG-traditional obesity indices, while the improvement for TyG-novel obesity indices ranged from - 1% to 16% and 5%-19%, respectively. In summary, all TyG-traditional obesity indices demonstrated strong associations with CMM, whereas among the TyG-novel obesity indices, only TyG-CVAI showed a similarly strong association. Furthermore, all TyG-related parameters showed significantly increased hazard ratios in their highest-exposure or poor-control status versus the reference (lowest exposure or good control): TyG-index (1.69/2.05), TyG-WC (2.24/2.28), TyG-WHtR (1.92/2.05), TyG-BMI (1.85/2.27), TyG-CVAI (1.89/2.07), TyG-BRI (1.94/2.08), TyG-ABSI (1.70/1.85), and TyG-WWI (1.97/1.95). Predictive analyses showed that, except for TyG index, TyG-ABSI and TyG-WWI, all other TyG-related parameters provided a certain degree of net improvement compared with the baseline risk model.

Conclusion: All eight TyG-related parameters can predict the incidence of CMM. Given their relative simplicity, the TyG-traditional obesity indices demonstrate superior incremental risk assessment and predictive value for CMM compared to the TyG-novel obesity indices and the TyG index, positioning them as promising and more practical tools for clinical practice.

Background: In recent years, amidst the phase-out of long-chain per- and polyfluoroalkyl substances (PFAS), the true relationship between PFAS exposure and lipid metabolism or cardiovascular disease (CVD), as well as the role of lipid profiles in this association, remains unclear.

Methods: Data from 25 531 NHANES participants (age ≥ 20 years old) enrolled between 2015 and 2020 were examined. To assess links between individual PFAS and cardiovascular disease (CVD) as well as lipid measures, both logistic and multivariable linear regression analyses were performed. Nonlinear exposure-response patterns with CVD were fitted using restricted cubic splines. In addition, the combined impact of PFAS mixtures on CVD risk was investigated via Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression, and quantile g-computation (Q-gcomp), and mediation analyses were evaluated using causal mediation models.

Results: After comprehensive adjustment, each log-unit increase in PFNA, n-PFOA, n-PFOS, and Sm-PFOS was inversely associated with CVD risk. There was a significant inverse trend in the associations of n-PFOA and Sm-PFOS with CVD. PFDeA, PFHxS, PFNA, PFUA, n-PFOA, n-PFOS, and Sm-PFOS were significantly positively associated with total cholesterol (TC). PFUA was significantly negatively associated with triglycerides (TG), and specific PFAS also showed significant positive associations with low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Mixture exposure analysis indicated a significant inverse trend between PFAS mixtures and CVD, with Sm-PFOS contributing the most weight in the mixture index. Through mediation analysis, we found that total cholesterol and LDL cholesterol serve as significant intermediaries in the relationships between PFNA, n-PFOA, n-PFOS, Sm-PFOS, and cardiovascular disease.

Conclusion: These findings imply that contemporary PFAS exposure profiles may confer differential cardiovascular effects, in part through lipid-mediated pathways, and highlight the need for continued monitoring and mechanistic studies to inform risk assessment and regulatory decisions.

Background/objectives: This study investigated the metabolic and pathological effects of a high-fat diet (HFD) in db/db mice and evaluated the therapeutic efficacy of various Coenzyme Q10 (CoQ10) products. We aimed to determine whether HFD-induced mitochondrial damage can be improved by different CoQ10 products through either repairing mitochondrial injury or increasing mitochondrial bioenergy, thereby addressing the root cause of oxidative stress.

Methods and results: Plasma biochemical analyses revealed that HFD induced hyperglycemia, elevated hepatic transaminases [aspartate aminotransferase (AST), alanine aminotransferase (ALT)], and dyslipidemia. Lecithin coenzyme Q10 (SoQ10) significantly improved these parameters, especially in reducing AST (255 ± 73.8 U/L vs. 138 ± 29.4 U/L, p < 0.05), ALT (87.8 ± 17.3 U/L vs. 79.2 ± 11.9 U/L, p < 0.05), and triglyceride levels (142.0 ± 37.0 mg/dL vs. 15.5 ± 2.5 mg/dL, p < 0.05), demonstrating greater efficacy than standard CoQ10. Histological evaluation showed that HFD caused marked hepatic steatosis and inflammatory infiltration. Oil Red O staining further confirmed excessive lipid deposition in the livers of HFD-fed mice. Both Q10 treatments decreased lipid droplet accumulation (p < 0.05), with SoQ10 showing a greater reduction (p < 0.05), indicating its potential to alleviate hepatic steatosis. Further assessments indicated that gene expression analyses showed that HFD upregulated lipid metabolism-related genes [lipoprotein lipase (LPL), peroxisome proliferator-activated receptor-γ (PPAR-γ), sterol regulatory element-binding protein-1 (SREBP-1), alkaline ceramidase 2 (ACER2)] (p < 0.05), indicating an imbalance between lipogenesis and lipolysis. SoQ10 modulated these genes and further enhanced ceramide synthase 2 (CERS2) expression, suggesting a role in reestablishing hepatic lipid homeostasis. Additionally, SoQ10 significantly upregulated genes associated with mitochondrial biogenesis peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), mitochondrial transcription factor A (TFAM)] (p < 0.05) and mitochondrial dynamics [mitofusin-2 (MFN2), optic atrophy type 1 long isoform (OPA1-L)] as well as fission [dynamin-related protein 1 (DRP1), mitochondrial fission protein 1 (Fis1)] (p < 0.05), indicating a potential to restore mitochondrial structural balance. In contrast, conventional CoQ10 had a more limited effect, particularly on fusion-related gene expression.

Conclusions: SoQ10 demonstrated superior therapeutic potential over conventional CoQ10 in ameliorating hepatic metabolic dysfunction, oxidative mitochondrial damage, and disturbances in lipid metabolism and mitochondrial dynamics induced by a high-fat diet.

Background: Rapid life rhythms have seen an increased participation in the weekend warrior pattern, but its impact on mortality risk in adults with metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. This investigation aims to explore the link between physical activity (PA) patterns, along with leisure-time and occupational physical activity (LTPA/OPA), as well as mortality in adults with MASLD.

Methods: This prospective cohort study employed data sourced from National Health and Nutrition Examination Survey (NHANES), and mortality data were collected through December 31, 2019. PA was self-reported and divided into four classifications: inactive, insufficiently active, weekend warrior, along with regularly active.

Results: Among 13,831 MASLD participants [mean (SD) age, 51.09 (16.63) years; 48.82% male], 1,191 deaths occurred in a median follow-up spanning 6.42 years. Compared to inactive participants, HR (95% CI) for all-cause mortality associated with LTPA and OPA were 0.66 (0.44 to 0.99) and 0.50 (0.30 to 0.84) in the weekend warriors, 0.63 (0.50 to 0.79) and 0.56 (0.43 to 0.72) in the insufficiently active, and 0.55 (0.43 to 0.71) and 0.62 (0.49 to 0.79) in the regularly active. Joint analyses revealed that LTPA and OPA had synergistic advantages in reducing the hazard of all-cause mortality with inactive group as the reference.

Conclusions: Adults engaging in active PA patterns - whether classified as insufficient, weekend warriors, or regularly active - exhibited lower all-cause mortality rates compared to inactive participants with MASLD. For those who can't adhere to daily exercise regimens, adopting a "weekend warrior" approach provides a practical and feasible strategy to curb the progression of MASLD and reduce the risk of premature mortality linked to it. Furthermore, public health guidelines should integrate both LTPA and OPA to achieve sustainable improvements in health outcomes across the population.

Objective: To investigate the associations between longitudinal body roundness index (BRI) trajectories and the risk of incident diabetes mellitus (DM) using data from the China Health and Retirement Longitudinal Study (CHARLS).

Methods: Group-based trajectory modeling (GBTM) identified distinct BRI trajectories (Waves 1-3, 2011-2016). Their associations with DM incidence (Wave 4, 2017-2018) were assessed using multivariate Cox models. The predictive performance of a single baseline BRI was compared with body mass index (BMI) and waist circumference (WC) via receiver operating characteristic (ROC) analysis. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) evaluated the incremental value of adding BRI trajectories to a conventional risk model. Subgroup and sensitivity analyses, including a landmark approach, assessed robustness.

Results: Among 4,150 participants, 103 developed DM. Three stable BRI trajectories were identified: low-stable (49.0%), moderate-stable (41.3%), and high-stable (9.7%). Compared with the low-stable group, the high-stable group had a significantly increased DM risk with a fully-adjusted hazard ratio (HR) of 2.63 (95% confidence interval [CI]: 1.41-4.91). A single baseline BRI showed comparable discrimination to BMI and WC (AUC ≈ 0.63). Longitudinal trajectories of BRI, BMI, and WC all identified high-stable subgroups with elevated risk (HRs: BRI = 2.63, BMI = 2.16, WC = 2.31), with overlapping confidence intervals. However, adding BRI trajectories to a conventional model significantly improved risk reclassification (NRI = 10.76%, 95% CI: 2.40-19.47) and discrimination (IDI = 0.27%, 95% CI: 0.03-0.52). Results were consistent across subgroups and sensitivity analyses.

Conclusions: Sustained high BRI exposure, captured by longitudinal trajectory modeling, is independently associated with increased DM risk. While BRI trajectories were not statistically superior to BMI or WC trajectories, the longitudinal framework itself adds value over single-time-point assessments by more robustly identifying individuals with persistent high adiposity-related risk, highlighting the utility of monitoring long-term body shape stability for early risk stratification.