Yongdi Zuo, Lei Chen, Manrong He, Jingxue Du, Wanxin Tang
{"title":"脂肪酸去饱和酶1 （FADS1）通过极低密度脂蛋白对慢性肾脏疾病的影响：一项药物靶标相关的孟德尔随机化研究","authors":"Yongdi Zuo, Lei Chen, Manrong He, Jingxue Du, Wanxin Tang","doi":"10.1016/j.jacl.2025.06.024","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease (CKD) is a globally prevalent condition and still lacks effective specific medications. Metabolic dysregulation plays a crucial role in CKD.</p><p><strong>Objective: </strong>To Identify new potential targets for CKD through metabolites and their regulatory genes.</p><p><strong>Methods: </strong>A total of 233 metabolites from the GWAS Catalog were utilized for Mendelian randomization (MR) with CKD. External validation was conducted from UK Biobank. Cis-eQTL of genes related to very low-density lipoprotein (VLDL) were selected for MR with CKD and metabolites. The total effect of the fatty acid desaturase 1 gene (FADS1) on CKD and metabolite-mediated effects were calculated. Bulk RNA-seq were used to validate FADS1 expression in the kidney tissues of patients with CKD.</p><p><strong>Results: </strong>The cholesteryl esters to total lipids ratio in medium VLDL (odds ratio [OR] = 0.84; P.adj = .039) and total cholesterol to total lipids ratio in small VLDL (OR = 0.84; P.adj = .003) were protective factors for CKD, whereas the triglycerides to total lipids ratio in small VLDL (OR = 1.18; P.adj = .009) and the triglycerides to total lipids ratio in very small VLDL (OR = 1.1; P.adj < .001) were risk factors. They mediated the risk of CKD by FADS1 (OR = 1.1; P.adj = .001), and mediation effects of 21.17%, 10.43%, 23.52%, and 29.96%, respectively, were obtained. The differential expression of FADS1 was observed in the kidney tissues of patients with CKD.</p><p><strong>Conclusion: </strong>FADS1 is a risk factor for CKD and a novel therapeutic target. Four metabolites mediate the detrimental effect of FADS1 in CKD.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of fatty acid desaturase 1 (FADS1) on chronic kidney disease via very low-density lipoprotein: A drug target-related mediation Mendelian randomization study.\",\"authors\":\"Yongdi Zuo, Lei Chen, Manrong He, Jingxue Du, Wanxin Tang\",\"doi\":\"10.1016/j.jacl.2025.06.024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Chronic kidney disease (CKD) is a globally prevalent condition and still lacks effective specific medications. Metabolic dysregulation plays a crucial role in CKD.</p><p><strong>Objective: </strong>To Identify new potential targets for CKD through metabolites and their regulatory genes.</p><p><strong>Methods: </strong>A total of 233 metabolites from the GWAS Catalog were utilized for Mendelian randomization (MR) with CKD. External validation was conducted from UK Biobank. Cis-eQTL of genes related to very low-density lipoprotein (VLDL) were selected for MR with CKD and metabolites. The total effect of the fatty acid desaturase 1 gene (FADS1) on CKD and metabolite-mediated effects were calculated. Bulk RNA-seq were used to validate FADS1 expression in the kidney tissues of patients with CKD.</p><p><strong>Results: </strong>The cholesteryl esters to total lipids ratio in medium VLDL (odds ratio [OR] = 0.84; P.adj = .039) and total cholesterol to total lipids ratio in small VLDL (OR = 0.84; P.adj = .003) were protective factors for CKD, whereas the triglycerides to total lipids ratio in small VLDL (OR = 1.18; P.adj = .009) and the triglycerides to total lipids ratio in very small VLDL (OR = 1.1; P.adj < .001) were risk factors. They mediated the risk of CKD by FADS1 (OR = 1.1; P.adj = .001), and mediation effects of 21.17%, 10.43%, 23.52%, and 29.96%, respectively, were obtained. The differential expression of FADS1 was observed in the kidney tissues of patients with CKD.</p><p><strong>Conclusion: </strong>FADS1 is a risk factor for CKD and a novel therapeutic target. Four metabolites mediate the detrimental effect of FADS1 in CKD.</p>\",\"PeriodicalId\":15392,\"journal\":{\"name\":\"Journal of clinical lipidology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-07-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of clinical lipidology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jacl.2025.06.024\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of clinical lipidology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jacl.2025.06.024","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Impact of fatty acid desaturase 1 (FADS1) on chronic kidney disease via very low-density lipoprotein: A drug target-related mediation Mendelian randomization study.
Background: Chronic kidney disease (CKD) is a globally prevalent condition and still lacks effective specific medications. Metabolic dysregulation plays a crucial role in CKD.
Objective: To Identify new potential targets for CKD through metabolites and their regulatory genes.
Methods: A total of 233 metabolites from the GWAS Catalog were utilized for Mendelian randomization (MR) with CKD. External validation was conducted from UK Biobank. Cis-eQTL of genes related to very low-density lipoprotein (VLDL) were selected for MR with CKD and metabolites. The total effect of the fatty acid desaturase 1 gene (FADS1) on CKD and metabolite-mediated effects were calculated. Bulk RNA-seq were used to validate FADS1 expression in the kidney tissues of patients with CKD.
Results: The cholesteryl esters to total lipids ratio in medium VLDL (odds ratio [OR] = 0.84; P.adj = .039) and total cholesterol to total lipids ratio in small VLDL (OR = 0.84; P.adj = .003) were protective factors for CKD, whereas the triglycerides to total lipids ratio in small VLDL (OR = 1.18; P.adj = .009) and the triglycerides to total lipids ratio in very small VLDL (OR = 1.1; P.adj < .001) were risk factors. They mediated the risk of CKD by FADS1 (OR = 1.1; P.adj = .001), and mediation effects of 21.17%, 10.43%, 23.52%, and 29.96%, respectively, were obtained. The differential expression of FADS1 was observed in the kidney tissues of patients with CKD.
Conclusion: FADS1 is a risk factor for CKD and a novel therapeutic target. Four metabolites mediate the detrimental effect of FADS1 in CKD.
期刊介绍：
Because the scope of clinical lipidology is broad, the topics addressed by the Journal are equally diverse. Typical articles explore lipidology as it is practiced in the treatment setting, recent developments in pharmacological research, reports of treatment and trials, case studies, the impact of lifestyle modification, and similar academic material of interest to the practitioner.
Sections of Journal of clinical lipidology will address pioneering studies and the clinicians who conduct them, case studies, ethical standards and conduct, professional guidance such as ATP and NCEP, editorial commentary, letters from readers, National Lipid Association (NLA) news and upcoming event information, as well as abstracts from the NLA annual scientific sessions and the scientific forums held by its chapters, when appropriate.
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