Lipids in Health and Disease最新文献

Background: Vascular calcification (VC) is highly prevalent in patients undergoing maintenance hemodialysis (MHD) and is associated with cardiovascular morbidity. However, traditional lipid and mineral markers have limited predictive value. Y-box binding protein-1 (YB-1), a regulator of lipid metabolism and inflammation, may provide additional mechanistic and clinical insight.

Methods: Serum YB-1 was measured in 209 MHD patients (30-month follow-up) who were stratified into hyperlipidemia and control groups. Receiver Operating Characteristic (ROC) and decision curve analysis (DCA, threshold range 0.1-0.4) were used to assess the predictive performance of YB-1 against traditional models based on lipid, glucose, and bone metabolism. Mechanistic studies in HL-60-derived neutrophil-like cells and a 5/6 nephrectomized rat model were performed to assess the role of YB-1 in neutrophil extracellular trap (NET) formation and VC.

Results: Serum YB-1 was significantly elevated in hyperlipidemia patients and was independently associated with new-onset VC (AUC 0.707, 95% CI 0.630-0.784). YB-1 outperformed lipid-, glucose-, and bone-based models, providing added net clinical benefit in DCA within the 0.24-0.33 threshold range. Mechanistically, serum levels of citrullinated histone H3 (citH3), a NET marker, were increased in hyperlipidemia patients. In vitro, YB-1 and IS synergistically enhanced neutrophil lipid droplet accumulation and citH3 release, while NET-rich supernatants promoted VSMC calcification. In vivo, IS-treated 5/6 nephrectomy rats displayed elevated YB-1, increased citH3, and aggravated aortic calcification.

Conclusion: Serum YB-1 is a novel predictor and potential mechanistic mediator of VC in MHD patients. Incorporating YB-1 into existing clinical risk models may support earlier recognition of individuals at elevated cardiovascular risk and inform more effective management strategies to improve long-term health outcomes.

Background: Lipids play crucial roles in maternal and foetal metabolism; however, their effects on birth weight remain unclear. Moreover, the potential mediating role of inadequate gestational weight gain (iGWG) in this association remains unexplored. The objective of this study was to assess maternal lipid profiles in the third trimester and their associations with the risk of small-for-gestational-age (SGA) infants, focusing on the combined effects of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). This study also examined whether iGWG influenced this relationship.

Methods: Data were sourced from the Tongji Maternal and Child Health Cohort. Maternal fasting lipid levels were measured during the third trimester and birth information was retrieved from medical records. Log-Poisson regression analysis was performed to assess the relationship between lipid tertiles and SGA risk. The possible mediating role of iGWG was examined using the mediation package in R.

Results: An increased risk of SGA was associated with high HDL-C levels (adjusted relative risk [aRR], 1.54; 95% confidence interval [CI], 1.15-2.07), particularly among mothers with high HDL-C and low TG levels (aRR, 1.77; 95% CI, 1.10-2.87). This association remained significant among individuals with normal pre-pregnancy weight. The relationship between lipid profiles and SGA was independent of iGWG.

Conclusions: An increased risk of SGA was associated with high maternal HDL-C levels. The combination of low TG and high HDL-C levels was identified as a significant predictor of SGA. iGWG did not explain these associations.

Diabetic kidney disease (DKD), the predominant microvascular complication of diabetes mellitus, perpetuates a significant global health and socioeconomic challenge, complicating the pursuit of sustainable renal care. Adipokines, bioactive proteins secreted by adipose tissue that modulate lipid metabolism, function as key modulators potentially integrating systemic metabolic and inflammatory signals with renal pathophysiology Mechanistic investigations reveal that adipokines orchestrate a range of interconnected pathways, which include metabolic dysregulation (characterized by insulin resistance and lipid overload), immune-inflammatory responses (mediated by nuclear factor kappa B [NF-κB], NLR family pyrin domain containing 3 [NLRP3], and chemokine axes), oxidative stress coupled with mitochondrial dysfunction (involving adenosine monophosphate-activated protein kinase [AMPK] and peroxisome proliferator-activated receptor gamma coactivator 1-alpha [PGC-1α], reactive oxygen species [ROS]), endothelial dysfunction, fibrogenesis (driven by transforming growth factor beta [TGF-β]/Smad and epithelial-mesenchymal transition [EMT]), and the imbalance between apoptosis and autophagy. Protective adipokines such as adiponectin, irisin, and vaspin may mitigate harmful signaling, whereas leptin, resistin, visfatin, and chemerin could amplify injury through pro-inflammatory, pro-fibrotic, and lipotoxic pathways. Both circulating and urinary levels of adipokines may correlate with proteinuria, which suggests their potential utility in early detection, risk stratification, or therapeutic monitoring, although further validation is required.Emerging pharmacological, genetic, and lifestyle interventions may modulate adipokine networks to confer renal protection. The integration of multi-omics approaches, single-cell analysis, and spatial profiling with models that closely mimic human physiology is essential for identifying key signaling nodes, validating biomarkers, and developing precision-targeted therapies. Collectively, a detailed, network-oriented understanding of lipid-regulating adipokines could support efforts toward the development of personalized prevention and treatment strategies in DKD.

Background: Cardiometabolic multimorbidity (CMM) poses a major health burden in aging populations. The long-term effect of cumulative remnant cholesterol inflammatory index (RCII) on CMM remains unclear. This study aimed to examine this relationship among middle-aged and older Chinese adults.

Methods: This retrospective longitudinal cohort included 5,150 participants aged ≥ 45 years without baseline CMM from the China Health and Retirement Longitudinal Study. The cumulative average natural log-transformed RCII (cumlnRCII) was calculated from 2011 to 2015. RCII was defined as (remnant cholesterol × high-sensitivity C-reactive protein)/10. Incident CMM was defined as the new onset of at least two of the following conditions: diabetes, heart disease, or stroke by 2018. Multivariate Cox and logistic models were used to estimate the hazard ratio (HR) and odds ratio (OR), with restricted cubic splines used to test dose-response relationships. Subgroup and sensitivity analyses were conducted to ensure the reliability of the results.

Results: Over a median follow-up period of 7 years, 294 participants developed CMM. The incidence of CMM increased across cumlnRCII tertiles: 3.2% (Tertile 1), 5.2% (Tertile 2), and 8.7% (Tertile 3). After adjustment, compared with Tertile 1, Tertile 3 had significantly greater risks (OR = 2.14, 95% CI: 1.55-2.99; HR = 2.10, 95% CI: 1.53-2.89). Each 1-standard deviation increase in cumlnRCII was associated with a 33% higher odds and a 32% higher risk of CMM. A linear dose-response correlation was identified (P-nonlinear = 0.383). Most subgroups exhibited consistent associations, and sensitivity analyses validated the reliability of the results.

Conclusions: The cumulative average RCII is independently associated with increased CMM risk, underscoring its value for identifying high-risk individuals, guiding preventive strategies, and advancing efforts toward healthy aging by reducing the burden of cardiometabolic disease.

Background: Residual cardiovascular risk persists in patients with acute myocardial infarction (AMI) and hypertriglyceridaemia despite statin therapy. The potential benefit of acipimox, a niacin derivative, as an adjunct to statins in this context remains uncertain. This study evaluated the association between statin-acipimox combination therapy and cardiovascular outcomes in AMI patients with elevated triglyceride levels.

Methods: We conducted a retrospective cohort study using the Tianjin Coronary Artery Disease Specialised Database (2010-2024). First-time AMI patients with triglycerides ≥ 1.7 mmol/L who received statins were included. Patients treated with statins plus acipimox were compared with those receiving statin monotherapy. The primary outcomes were 1-year major adverse cardiovascular and cerebrovascular events (MACCE) and net adverse clinical events (NACE). Associations were first evaluated in the original unmatched cohort and then in a 1:1 propensity score-matched cohort. Subgroup analyses were prespecified. Sensitivity analyses included progressively adjusted Cox models, IPTW-adjusted repetitions, adherence-stratified analyses, and Fine-Gray competing risk models.

Results: Among 38,190 eligible AMI patients with hypertriglyceridaemia, 624 received acipimox in addition to statins. In the original unmatched cohort, combination therapy was associated with lower 1-year risks of MACCE (adjusted hazard ratio [aHR] 0.66, 95% confidence interval [CI] 0.49-0.87) and NACE (aHR 0.64, 95% CI 0.52-0.79), with no significant differences in all-cause or cardiac mortality. After 1:1 propensity score matching (596 pairs), these benefits persisted (MACCE: aHR 0.68, 95% CI 0.51-0.90; NACE: aHR 0.64, 95% CI 0.48-0.84), again without a mortality difference. Secondary analyses demonstrated larger reductions in triglycerides, LDL-C and VLDL-C and greater increases in HDL-C with combination therapy. Subgroup analyses showed generally consistent protective associations across most clinical strata. Subgroup findings were generally consistent across most strata. Results remained robust across all sensitivity analyses.

Conclusions: In this real-world cohort, adding acipimox to statin therapy was associated with improved cardiovascular outcomes in AMI patients with hypertriglyceridaemia, accompanied by a favourable downward trend in triglyceride-related lipid measures.