Lipids最新文献

Serine β-lactamase-like protein (LACTB), a mitochondrial protease, has incompletely characterized roles in metabolic pathways. We employed Mendelian randomization to investigate LACTB's causal relationships with lipid metabolism, metabolic syndrome (MetS), and chronic kidney disease (CKD). We performed a comprehensive Mendelian randomization (MR) analysis using genome-wide association study summary statistics. Cis-expression quantitative trait loci from the eQTLGen consortium identified genetic instruments for LACTB. Two-sample MR approaches, including inverse variance weighted, MR-Egger, and weighted median methods, were applied. The cisMR-conditional maximum likelihood (cisMR-cML) method validated LACTB-related causal associations. GTEx Portal data independently replicated the LACTB-CKD relationship. LACTB exhibited significant negative causal effects on metabolic syndrome (95% CI: 0.91-0.99, p = 0.02) and chronic kidney disease (95% CI: 0.83-0.97, p = 0.009). cisMR-cML validation confirmed significant causal associations between LACTB and lipid profiles after Bonferroni correction. Metabolic syndrome demonstrated a robust positive causal effect on CKD (95% CI: 1.15-1.42, p = 8.45 × 10^-6), with high-density lipoprotein showing a significant negative causal relationship with CKD (95% CI: 0.89-0.97, p = 0.0009). Mediation analysis revealed metabolic syndrome mediated 11.8% of the total effect between LACTB and CKD (mediation effect: -0.01, 95% CI: -0.024 to -0.0003). Our study elucidates LACTB's critical role in metabolic regulation, identifying a potential therapeutic target for preventing chronic kidney disease progression. By delineating complex interactions between LACTB, lipid metabolism, metabolic syndrome, and kidney function, we provide novel insights for precision medicine in metabolic and renal health.

Celiac disease (CD), an autoimmune disorder triggered by gliadin, is treated with a strict gluten-free diet. While omega-3 intake is known to reduce inflammation in other autoimmune diseases, its role in CD remains unclear due to limited data on fatty acid intake in this population. To assess the dietary intake of polyunsaturated fatty acids (PUFAs) in patients with CD compared with healthy controls. In this cross-sectional study, patients with CD and age- and sex-matched healthy controls were evaluated. Sociodemographic data and dietary intake were assessed using a validated food frequency questionnaire administered by a trained dietitian. Intakes of total fat, saturated, monounsaturated, polyunsaturated (omega-6 and omega-3) fatty acids, and micronutrients were analyzed along with the food sources of these fats. Compared with controls, CD patients had significantly higher intakes of total fat, saturated fat, total PUFA, omega-6, omega-3 (all p < 0.041), and calcium (p = 0.013), but lower iron intake (p < 0.020). The omega-6/omega-3 ratio did not differ between groups. Relative to FAO/WHO recommendations, CD patients consumed more energy, protein, cholesterol, zinc, vitamin B12, and fiber, but less trans fats, iron (p < 0.001), and vitamin D (p < 0.006). In both groups, omega-3 intake came mainly from fatty fish and lipid-rich foods, while omega-6 intake was primarily from oils. Both groups showed inadequate omega-3 intake, potentially predisposing them to low-grade inflammation. The findings suggest that optimizing fatty acid intake, particularly in gluten-free diets, may benefit CD patients and warrant further research.

Ischemic stroke is frequently associated with symptomatic intracranial atherosclerotic stenosis (sICAS), is a leading cause of global disability and mortality. Current guidelines recommend dual antiplatelet and intensive statin therapies. Proprotein convertase subtilisin 9/kexin type 9 (PCSK9) inhibitors have emerged as a potent lipid-lowering therapy, potentially influenced by genetic variations, particularly in the CYP2C19 gene. This study at Xuzhou Central Hospital from January 2021 to December 2023 included 151 patients divided into a statin group (n = 73) and a PCSK9 inhibitor (PCSK9i) group (n = 78). It evaluated lipid profiles, inflammatory markers, neurological function, and clinical outcomes over a 180-day follow-up period, with additional analysis stratified by CYP2C19 genotype. The PCSK9i group demonstrated significant improvements in lipid parameters compared to the statin group, including greater reductions in low-density lipoprotein cholesterol (LDL-C) (p = 0.008), total cholesterol (TC) (p < 0.001), and triacylglycerols (TAG) (p = 0.041), along with apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) (both p < 0.001). Inflammatory markers, particularly interleukin-6 (IL-6), significantly reduced in the PCSK9i group (p < 0.001). In the PCSK9i group, CYP2C19 rapid metabolizers achieved greater reductions in LDL-C (p = 0.021), ApoB (p = 0.003), and IL-6 levels (p = 0.041) compared to slow metabolizers. Post-treatment modified Rankin Scale (mRS) scores were significantly lower in rapid metabolizers compared to slow metabolizers (p = 0.018), though clinical events occurred infrequently in both subgroups. This study demonstrates that PCSK9 inhibitor therapy combined with statins provides enhanced lipid-lowering and anti-inflammatory effects compared to statin monotherapy in sICAS patients. While the CYP2C19 genotype may influence specific treatment responses, particularly lipid parameters, its impact on clinical outcomes requires further investigation.

As a cholesterol metabolite, cholesterol sulfate (CS) is widely distributed in the human body, and its role as a regulatory factor has been continuously explored from the 1980s to the present day. However, changes in CS in metabolic disorders have not been systematically investigated. Here, rodent models of insulin resistance, fatty liver, and atherosclerosis were established. The CS content, CS to cholesterol ratio, and CS to total bile acids (TBA) ratio in the serum and liver of these model mice were compared with those of normal mice. Results showed the CS content was increased in fatty liver and atherosclerosis models of mice; meanwhile, it might be influenced by genotype, such as CD36 deficiency. The changes in the CS to cholesterol ratio were related to the amount and distribution of cholesterol. Besides, there was competition between the catabolism of cholesterol to bile acids or CS, as evidenced by the opposite trend between the TBA to cholesterol ratio and the CS to TBA ratio. Moreover, for the first time, it has been discovered that CS is enriched in lipid droplets, which further substantiates the close association between CS and lipid metabolism. Building on studies that demonstrated the beneficial effects of CS supplementation in alleviating lipid metabolic disorders, we first proposed the hypothesis that an increase in CS content may be protective against lipid metabolic disorders. This study provided a new perspective on the role of CS as a regulatory factor in metabolic disorders.

This in silico network-pharmacology investigation delineates the molecular interplay linking statin-induced Coenzyme Q10 (CoQ10) deficiency to statin-associated muscle symptoms (SAMS). GeneCards-derived targets related to SAMS, CoQ10 deficiency, and statins were integrated, and the intersecting gene set was analyzed through STRING-based protein-protein interaction mapping, followed by hub-gene prioritization using CytoHubba. Functional enrichment via ShinyGO revealed that the 145 common genes converge predominantly on inflammatory, metabolic, and mitochondrial pathways. Tumor necrosis factor (TNF) emerged as a principal regulatory node, exerting influence through Mitogen-Activated Protein Kinase (MAPK)-mediated apoptotic and stress-response cascades that plausibly contribute to mitochondrial dysfunction, oxidative stress, impaired energy metabolism, and myocellular injury in the context of CoQ10 depletion. The constructed pathway-based interaction network illustrates how suppression of the mevalonate pathway by statins disrupts CoQ10 biosynthesis, sensitizing muscle tissue to cytokine-driven inflammatory signaling and amplifying apoptotic susceptibility. Collectively, the findings highlight the TNF-MAPK axis as a mechanistic core of SAMS pathophysiology and underscore the interconnected roles of immune activation, lipid metabolic imbalance, and mitochondrial impairment. These insights provide a molecular rationale for therapeutic strategies targeting mitochondrial preservation or inflammatory modulation, including CoQ10 supplementation, and reinforce the need for experimental and clinical validation to substantiate computationally derived predictions.

Primary dysmenorrhea (PD) has always been a significant clinical challenge affecting women's health. Traditional Chinese medicine (TCM) has attracted considerable research interest owing to its advantages of multiple target and multiple pathway. This study employed urinary lipidomics technology combined with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-O-TOF-MS) to systematically elucidate the preventive mechanisms and therapeutic targets of Danggui Shaoyao San (DSS) in a PD rat model. A total of 34 lipid biomarkers representing the dysregulated lipid metabolism in PD were preliminarily identified. Except for 3alpha-hydroxy-5beta-chola-7,9(11)-dien-24-oic acid and 16-oxoandrostenediol, all 32 lipids had high diagnostic significance. And then, the metabolic alterations related to DSS intervention through the regulation of lipid biomarkers and related pathways were discovered. Among the differentially expressed lipids, 29 lipid biomarkers were significantly restored by DSS administration. Through the pathway enrichment analysis, two key perturbation pathways related to DSS therapy were found, including arachidonic acid metabolism, and primary bile acid biosynthesis, which had the potential to become new therapeutic targets for treating PD. These investigations demonstrated that DSS may have a significant efficacy on the progression of PD by multi-target regulation of lipid biomarkers and lipidomics-guided biochemical pathways, providing a scientific foundation for its clinical application.

Dysregulated lipid metabolism fuels cancer progression through enhanced lipogenesis, cholesterol synthesis, and fatty acid oxidation. Herbal bioactives provide multi-targeted molecular interventions capable of restoring lipid homeostasis while minimizing toxicity. Guggulsterone (GS), a plant-derived steroidal compound from Commiphora mukul, exemplifies this paradigm by modulating key regulators such as ATP citrate lyase (ACLY), acetyl-CoA carboxylase (ACC), farnesoid X receptor (FXR), and AMP-activated protein kinase (AMPK). Through these actions, it suppresses oncogenic lipid signaling, reprograms the tumor microenvironment, and enhances apoptotic sensitivity. This article outlines the molecular underpinnings of GS's lipid-lowering and antitumor effects, emphasizing its potential as a pharmacological scaffold for metabolic reprogramming in cancer.

Elevated plasma lipoprotein(a) (Lp(a)) (> 125 nmol/L) is highly prevalent and a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) that may contribute significantly to plasma levels of low-density lipoprotein-cholesterol (LDL-C). This study aimed to describe clinical characteristics across Lp(a) levels and to estimate the proportion of individuals with normal, moderately elevated, or elevated LDL-C earlier in life according to levels of Lp(a), to assess whether LDL-C levels are a reliable marker for an underlying elevated Lp(a) level. In this retrospective study, detailed information on clinical characteristics was collected through medical records, while biochemical data was retrieved from the North Denmark Region Clinical Laboratory System (LABKA) I and II between January 2021 and August 2024. A total of 1346 individuals were included of whom 28.5% had elevated Lp(a) levels ≥ 125 nmol/L. A history of ASCVD was found in 57.7% of patients with Lp(a) levels ≥ 400 nmol/L compared to 21.1% of patients with Lp(a) levels < 100 nmol/L and the median age of onset of ASCVD was 51 years and 56 years, respectively. Furthermore, in individuals with Lp(a) levels ≥ 300 nmol/L, we found that 7.6% had LDL-C < 3.0 mmol/L and 9.1% had LDL-C between 3.0 and 3.5 mmol/L when measured for the first time, respectively. This study highlights distinct clinical characteristics across Lp(a) levels. With increasing Lp(a) levels, the prevalence of ASCVD increased, while the age at onset of ASCVD decreased. Furthermore, we found that LDL-C within the normal range cannot be used to rule out highly elevated Lp(a) levels.

The non-high-density lipoprotein cholesterol (non-HDL-c) to high-density lipoprotein cholesterol (HDL-c) ratio (NHHR) is an emerging and valuable biomarker for cardiovascular disease risk. Nevertheless, robust evidence regarding its relationship with both the prevalence and severity of albuminuria remains incompletely elucidated. This cross-sectional study analyzed data from the 1999 to 2018 US National Health and Nutrition Examination Survey to investigate the association between NHHR and albuminuria, assessed via the urinary albumin-to-creatinine ratio (uACR). Multivariate logistic and linear regression models, restricted cubic spline analysis, subgroup analyses and receiver-operating characteristic curve analysis were employed. Among the 14,376 participants included, the prevalence of microalbuminuria and macroalbuminuria was 6.83% and 1.06%, respectively. The adjusted odds ratios (95% confidence intervals) for each one-unit increase in NHHR were 1.09 (1.04-1.15) for any albuminuria, 1.06 (1.01-1.12) for microalbuminuria, and 1.23 (1.11-1.37) for macroalbuminuria. NHHR was positively correlated with uACR (β = 4.08, 95% confidence interval 1.11-7.04). Restricted cubic spline analysis revealed a positive association, which became more pronounced at NHHR levels exceeding 2.77. Subgroup analyses further demonstrated that this association was stronger in individuals with a body mass index ≥ 30 kg/m² or an estimated glomerular filtration rate ≥ 90 mL/min/1.73 m². Receiver-operating characteristic curve analysis confirmed that NHHR possessed superior discriminative power for albuminuria compared to conventional lipid parameters of total cholesterol, HDL-c, non-HDL-c, triglycerides, and apolipoprotein B. We concluded that elevated NHHR is positively and independently associated with an increased risk and severity of albuminuria, highlighting its clinical relevance as a potential biomarker, particularly among individuals with obesity and preserved renal function.

7-Ketocholesterol (7-KC), a cytotoxic oxysterol, contributes to atherosclerosis, neurodegeneration, and metabolic disorders by promoting oxidative stress, inflammation, and dysfunction of organelles including mitochondria, peroxisomes, lysosomes, and the endoplasmic reticulum, ultimately leading to cell death. Nutritional biomedicine offers potential strategies to counteract these effects using antioxidant nutrients and probiotics. In this study, genes associated with 7-KC toxicity were retrieved from GeneCards, and targets of quercetin, luteolin, butyrate, Docosahexaenoic Acid (DHA), and vitamin E were predicted using SwissTargetPrediction. Overlapping targets were identified via an interactive Venn tool and analyzed through STRING protein-protein interaction networks, CytoHubba hub ranking, and Gene Ontology (GO)/ClueGO pathway enrichment. Twenty shared genes were identified, with Peroxisome Proliferator-Activated Receptor Gamma (PPARG), AKT Serine/Threonine Kinase 1 (AKT1), Amyloid Precursor Protein (APP), and Matrix Metalloproteinase-9 (MMP9) as key hubs. Enriched processes included sterol metabolism, cholesterol efflux, inflammatory regulation, and organelle protection, indicating multi-target modulation. These findings support that combinatorial nutrient interventions can restore sterol homeostasis, mitigate oxidative stress, and attenuate 7-KC-induced pathologies.