Lipids最新文献

{"title":"Lipid-Soluble Signaling Molecular Model Predicts Prognosis and Immunotherapy Response in Gastric Cancer.","authors":"Wenwen Zhu, Yanna Yu","doi":"10.1002/lipd.70063","DOIUrl":"https://doi.org/10.1002/lipd.70063","url":null,"abstract":"<p><p>Lipid-soluble signaling molecule-related genes (LSMRGs) are critical in various tumors, but their role in gastric cancer (GC) prognosis and therapy remains unclear. Using transcriptomic data, this study analyzed LSMRG expression patterns, molecular subtypes, prognostic significance, and immune-microenvironment interactions in GC to identify new prognostic biomarkers and support precision medicine approaches. Using GC data from TCGA and GEO, LSMRGs from Genecard were analyzed. Unsupervised clustering defined LSMRG-based subtypes. Differentially expressed LSMRGs were identified by intersecting tumor-normal DEGs. A prognostic risk-score model was built via univariate Cox, LASSO, and multivariate Cox analyses, with model genes validated by qRT-PCR in cell lines. Comprehensive transcriptomic analyses included nomogram development, gene enrichment, immune infiltration, somatic mutations, and drug sensitivity. LSMRG-based clustering identified two patient subtypes with distinct survival and immunotherapy responses. From 83 differentially expressed LSMRGs, a 6-gene prognostic risk-score model was constructed, validated as an independent prognostic factor. Model gene expression was confirmed via qRT-PCR. The risk score accurately predicted 1-, 3-, and 5-year survival. High- and low-risk groups exhibited differential enrichment in pathways including neuroactive ligand-receptor interaction and hormone signaling. The high-risk group had a higher mutation burden, lower immune infiltration, and distinct drug sensitivity profiles compared to the low-risk group. This study delineates the expression landscape of LSMRGs in GC and clarifies their associations with molecular subtypes, prognosis, and immune regulation. The findings provide novel prognostic biomarkers and a molecular basis for targeting lipid-soluble signaling pathways in GC therapy.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Vitamin E on Lipid Profile in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Systematic Review and Meta-Analysis.","authors":"Mehdi Karimi, Maryam Abidi, Ayda Aghaei, Paris Kazemian, Negar Rafiezadeh Banadak, Ali Daneshmand Bahman, Omid Fakharzadeh Moghadam, Maryam Asadi Amin, Rana Kamali Khorgoo, Forough Sharifara, Mahsa Hosseini, Omid Asbaghi","doi":"10.1002/lipd.70042","DOIUrl":"https://doi.org/10.1002/lipd.70042","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with dyslipidemia and overweight. Vitamin E has been suggested to improve lipid metabolism, but clinical evidence in MASLD remains inconsistent. This meta-analysis evaluates the effects of vitamin E on serum lipid profiles and body mass index (BMI) in adults with MASLD. A literature search was conducted across databases through January 2026 to identify eligible randomized controlled trials (RCTs). Outcomes included triglycerides (TG), total cholesterol (TC), low- and high-density lipoprotein cholesterol (LDL-C & HDL-C), and BMI. Pooled effect estimates were calculated as weighted mean difference (WMD) with 95% confidence intervals (CIs) using a random-effects model. The pooled analysis of 12 RCTs showed that vitamin E in patients with MASLD significantly reduced TG (-12.74 mg/dL, 95% CI: [-22.78, -2.70], p = 0.013), whereas no significant change was observed in TC (-2.11 mg/dL, 95% CI: [-4.89, 0.67], p = 0.137) and LDL-C (-5.32 mg/dL, 95% CI: [-11.15, 0.51], p = 0.074), HDL-C levels (0.23 mg/dL, 95% CI: [-0.48, 0.94], p = 0.527), and BMI (0.36 kg/m², 95% CI: [-0.86, 1.58], p = 0.563). Subgroup analyses revealed that TG was significantly reduced in low-dose, more prolonged supplementation and in overweight patients. For TC, LDL-C, and HDL-C, only a slight, significant improvement was observed in patients with obesity. Vitamin E in patients with MASLD selectively modulates lipid metabolism, predominantly reducing TG levels. Modest improvements in TC, LDL-C, and HDL-C were observed primarily in patients with obesity. These findings support the potential role of vitamin E as an adjunctive therapy for MASLD-associated dyslipidemia.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Pharmacology Insights Into Statin-Induced Coenzyme Q10 Deficiency: Lipid Metabolic Crosstalk, TNF-MAPK Signaling, and Muscle Toxicity.","authors":"Nila Ganamurali, Sarvesh Sabarathinam","doi":"10.1002/lipd.70028","DOIUrl":"10.1002/lipd.70028","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":" ","pages":"299-307"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145714588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Hypothesis for the Protective Rise in Cholesterol Sulfate Against Lipid Metabolic Disorders.","authors":"Xiaoyue Li, Chengcheng Wang, Yuming Wang, Tiantian Zhang","doi":"10.1002/lipd.70031","DOIUrl":"10.1002/lipd.70031","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":" ","pages":"309-317"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of CYP2C19 Genotype Variants on PCSK9 Inhibitor Efficacy in Lipid-Lowering Among Patients With Symptomatic Intracranial Atherosclerotic Stenosis.","authors":"Chao Zhao, Nuan Wang, Di Shi, Hao Zhou, Dan Chen, Guofang Chen","doi":"10.1002/lipd.70018","DOIUrl":"10.1002/lipd.70018","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":" ","pages":"319-329"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eicosapentaenoic and Docosahexaenoic Acid Levels in Mouse Tissues After Intake of Echium and Ahiflower Oils Rich in Stearidonic and α-Linolenic Acids.","authors":"Letícia V Segre, Mariana S Bisinotto, Inar A Castro","doi":"10.1002/lipd.70041","DOIUrl":"10.1002/lipd.70041","url":null,"abstract":"<p><p>Omega-3 fatty acids (n-3 FA), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been consumed aiming to reduce cardiovascular disease. Fish oil is the main dietary source of EPA and DHA but has limitations that have stimulated interest in sustainable alternatives such as Echium ( Echium plantagineum ) and Ahiflower ( Buglossoides arvensis ) oils, both rich in α-linolenic acid (ALA) and stearidonic acid (SDA), precursors of EPA. However, the ability of these two oils to increase EPA and DHA levels in different tissues remains unclear. Thus, this study aimed to investigate the effects of SDA-rich oils on fatty acid profiles in different biological matrices of C57BL/6 mice. Animals received diets supplemented with soybean oil (control), Echium oil, or Ahiflower oil (4% diet) for 8 weeks, providing n-3/n-6 FA intake ratios of 0.14, 1.51, and 2.28, respectively. Fatty acids were analyzed in plasma, erythrocytes, liver, adipose tissue, heart, and brain. Both SDA-rich oils significantly increased EPA levels across all tissues in a dose-dependent manner compared with the control, whereas changes in DHA were limited and tissue-specific. Despite the increase in EPA, DHA levels remained unchanged in the heart, brain, and plasma. In erythrocytes, DHA levels were higher in both SDA-rich oil groups compared with the control. Echium and Ahiflower oils may be strategically used in EPA-focused interventions and, depending on the target tissue and physiological demand, may partially satisfy DHA requirements. This nuanced understanding is critical for the development of evidence-based dietary recommendations and sustainable omega-3 supplementation strategies.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":" ","pages":"417-426"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Lipid Biology-Associated Gene Expression in Granulosa Cells in Hyperandrogenic PCOS: A Possible Link Between Dyslipidemia and Hyperandrogenism.","authors":"Caglar Berkel","doi":"10.1002/lipd.70035","DOIUrl":"https://doi.org/10.1002/lipd.70035","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a heterogeneous reproductive endocrine condition in women, with implications in fertility and long-term metabolic health. PCOS with hyperandrogen (HA-PCOS; hyperandrogenic PCOS) has been recently identified as one of the four subtypes of PCOS. Dyslipidemia is known to be associated with clinical hyperandrogenism in PCOS. Indeed, patients with HA-PCOS were found to have the highest incidence of dyslipidemia among patients with the other three subtypes of PCOS. In the present study, we identified genes involved in lipid-associated processes (namely, lipid biosynthetic process, lipid catabolic process, hyperlipidemia, hypolipidemia and lipid homeostasis) whose expression are changed in granulosa cells from HA-PCOS patients compared to those from non-PCOS women, in order to identify molecular factors contributing to the highest risk of dyslipidemia incidence observed in patients with hyperandrogenic PCOS. We found 27 lipid biology-associated genes (ACSM1, ACSM3, AGPAT4, AJUBA, ALDH1A2, CCDC3, LPL, P2RX1, PITPNM1, PRLR, PTGIS, SLC44A5, SPTSSB, ST8SIA5, IDH1, ITPKA, PPM1L, SPTLC2, ADRA2A, ASPG, IRS1, PLB1, IDH1, LCT, NUDT8, SMPDL3A and SYNE2) whose transcript levels are significantly downregulated or upregulated in granulosa cells of women with HA-PCOS compared to those in control women. The majority of these genes have not been previously studied in the context of PCOS, and are possible candidates for further research to better understand the contribution of high androgen levels to dyslipidemia in PCOS. Targeting of high androgen-induced dyslipidemia might be of high clinical importance in the treatment of women with HA-PCOS.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"61 3","pages":"363-370"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral versus Marrow Lipidomics in Patients with Severe Aplastic Anemia: Potential Indicators for Early Immunosuppressive Treatment Response.","authors":"Zexing Sun, Yilei Hong, Yaonan Hong, Chuanao Xin, Qi Liu, Huijin Hu, Yingying Shen, Ying Chen, Shan Liu, Yiping Shen, Yuhong Zhou, Dijiong Wu","doi":"10.1002/lipd.70034","DOIUrl":"10.1002/lipd.70034","url":null,"abstract":"<p><p>This study aimed to explore the differences of peripheral blood (PB) and bone marrow serum lipidomic profiles in severe aplastic anemia (SAA) patients and their significance in predicting earlier immunosuppressive therapy (IST) response. A cohort of 11 newly diagnosed SAA patients and 15 healthy controls were enrolled between June 2020 and November 2022, and six of the SAA patients received ATG-based IST. PB and BM serum were collected for further LC-MS/MS analysis. Compared to donors, SAA patients exhibited more pronounced abnormalities in lipid metabolism profiles within BM serum relative to PB serum. Specifically, elevated levels of free fatty acids (FA), fatty acid esters of hydroxyl fatty acids (FAHFA), and phosphatidylserine (PS) were noted in the BM serum of SAA patients. Following treatment, there was a noted increase in acylcarnitine (ACar), hexosylceramide non-hydroxy fatty acid-sphingosine (HexCer-NS), and sulfur hexosyl ceramide hydroxy fatty acid (SHexCer), while levels of lysophosphatidylcholine (LPC) and oxidized phosphatidylcholine (OxPC) diminished, particularly in complete or partial response (CR/PR) patients. Acknowledging the changes of BM lipidomics may contribute to earlier prediction of ATG-based IST response in SAA patients.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":" ","pages":"347-361"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guggulsterone, a Classical Lipid-Lowering Phytosteroidal FXR Antagonist, as a Modulator of Lipid Signaling and Metabolic Reprogramming in Cancer.","authors":"Nila Ganamurali, Mohanapriya Devarajan, Sarvesh Sabarathinam","doi":"10.1002/lipd.70030","DOIUrl":"10.1002/lipd.70030","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":" ","pages":"279-284"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Insights Into the Central Role of Serine β-Lactamase-Like Protein in Lipid Metabolism, Metabolic Syndrome, and Chronic Kidney Disease.","authors":"Han Xu, Mengxiao Zou, Yichun Cheng, Shuwang Ge","doi":"10.1002/lipd.70032","DOIUrl":"10.1002/lipd.70032","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":" ","pages":"339-346"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}