Journal of Lipid Research最新文献

{"title":"Helminth-induced prostaglandin signaling and dietary shifts in PUFA metabolism promote colitis-associated cancer.","authors":"Katherine A Smith, Ella K Reed, Irina Guschina, Victoria J Tyrrell, Claire Butters, Matthew G Darby, Brunette Katsandegwaza, Alisha Chetty, William G C Horsnell, Valerie B O'Donnell, Awen Gallimore","doi":"10.1016/j.jlr.2025.100837","DOIUrl":"10.1016/j.jlr.2025.100837","url":null,"abstract":"<p><p>Oxylipins derived from dietary polyunsaturated fatty acids (PUFAs) are key determinants of intestinal health, homeostasis, and inflammatory disorders, such as colitis-associated colorectal cancer. Previous research has independently linked a high dietary omega (ω)-6:ω-3 PUFA ratio, or intestinal helminth infection, to an increased risk of colitis-associated colorectal cancer. However, whether these two factors interact to exacerbate disease risk and whether oxylipins contribute to this is unknown. In this study, we report that infection with the helminth Heligmosomoides polygyrus bakeri (Hpb) exacerbates tumor formation when combined with a high ω-6:ω-3 PUFA ratio diet. Dietary increases in tumor burden correlated with heightened levels of arachidonic acid (AA) and AA-derived lipoxygenase (LOX) oxylipins in the colon, including the 12/15-LOX product 12-hydroxyeicosatetraenoic acid, prior to disease onset. Although helminth infection further increased the production of 12/15-LOX oxylipins and increased expression of Alox15, responsible for producing these metabolites, inhibition of cyclooxygenase-dependent prostaglandin production with aspirin prevented helminth-exacerbation of disease. Helminth-infected mice exhibited increased phosphorylation of β-catenin in the colon, which was inhibited by EP2 and 4 antagonists. Moreover, administration of an EP agonist increased tumor burden in naive mice fed a high ω-6:ω-3 PUFA ratio diet, to the levels seen in helminth-exacerbation of disease. These data suggest that dietary changes in fatty acid composition coordinate with helminth-induced activation of EP signaling to exacerbate tumor development.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100837"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial calcium uniporter is required for thermogenic adaptation mediated by reactive oxygen species signaling.","authors":"Suji Kim, Seung-Kuy Cha, Kyu-Sang Park, Jun Namkung","doi":"10.1016/j.jlr.2025.100834","DOIUrl":"10.1016/j.jlr.2025.100834","url":null,"abstract":"<p><p>Mitochondrial Ca²⁺ influx via mitochondrial calcium uniporter (MCU) accelerates mitochondrial biogenesis and energy metabolism. Nevertheless, the molecular mechanism of MCU-dependent mitochondrial activation and thermogenesis in thermogenic adipose tissues remains elusive. In this study, we demonstrate that MCU governs mitochondrial functions in brown and beige adipocytes via the formation of mitochondrial reactive oxygen species (mtROS). Mice with a brown adipose tissue-specific Mcu knockout (Mcu BKO) mice exhibited decreased oxygen consumption and heat production, accompanied by downregulation of genes related to β-oxidation and thermogenesis. Furthermore, Mcu BKO mice, exhibiting a reduction in mtROS, showed defective thermogenic responses to cold exposure or β-adrenergic stimulation. Downregulation of thermogenic genes including Ucp1 in Mcu BKO mice can be rescued by exogenous ROS through AMP-activated protein kinase (AMPK) activation. Collectively, our findings suggest that MCU modulates mtROS-mediated mitonuclear signaling in thermogenic adipocytes.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100834"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucosylated cholesterol accumulates in atherosclerotic lesions and impacts macrophage immune response.","authors":"André R A Marques, Inês S Ferreira, Quélia Ribeiro, Maria J Ferraz, Elizeth Lopes, Daniela Pinto, Michael Hall, José Ramalho, Marta Artola, Manuel S Almeida, Gustavo Rodrigues, Pedro Araújo Gonçalves, Jorge Ferreira, Cláudia Borbinha, João Pedro Marto, Miguel Viana-Baptista, Ryan Gouveia E Melo, Luís Mendes Pedro, Maria I L Soares, Winchil L C Vaz, Otília V Vieira, Johannes M F G Aerts","doi":"10.1016/j.jlr.2025.100825","DOIUrl":"10.1016/j.jlr.2025.100825","url":null,"abstract":"<p><p>Atherosclerosis can be described as a local acquired lysosomal storage disorder (LSD), resulting from the build-up of undegraded material in lysosomes. Atherosclerotic foam cells accumulate cholesterol (Chol) and glycosphingolipids (GSLs) within lysosomes. This constitutes the ideal milieu for the formation of a side product of lysosomal storage: glucosylated cholesterol (GlcChol), previously found in several LSDs. Using LC-MS/MS, we demonstrated that GlcChol is abundant in atherosclerotic lesions. Patients suffering from cardiovascular diseases presented unaltered plasma GlcChol levels but slightly elevated GlcChol/Chol ratios. Furthermore, we mimicked GlcChol formation in vitro by exposing macrophages (Mφ) to a pro-atherogenic oxidized cholesteryl ester, an atherosclerosis foam cell model. Additionally, Mφ exposed to GlcChol exhibited an enlarged and multinucleated phenotype. These Mφ present signs of decreased proliferation and reduced pro-inflammatory capacity. Mechanistically, the process seems to be associated with activating the AMPK signaling pathway and the cyclin-dependent kinase inhibitor 1 (CDKN1A/p21), in response to DNA damage inflicted by reactive oxygen species (ROS). At the organelle level, exposure to GlcChol impacted the lysosomal compartment, resulting in the activation of the mTOR signaling pathway and lysosomal biogenesis mediated by the transcription factor EB (TFEB). This suggests that high concentrations of GlcChol impact cellular homeostasis. In contrast, under this threshold, GlcChol formation most likely represents a relatively innocuous compensatory mechanism to cope with Chol and GSL build-up within lesions. Our findings demonstrate that glycosidase-mediated lipid modifications may play a role in the etiology of genetic and acquired LSDs, warranting further investigation.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100825"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conjugated bile acids are elevated in severe calcific aortic valve stenosis.","authors":"Hannah Zhang, Negar Atefi, Arun Surendran, Jun Han, David R Goodlett, Davinder S Jassal, Ashish Shah, Amir Ravandi","doi":"10.1016/j.jlr.2025.100830","DOIUrl":"10.1016/j.jlr.2025.100830","url":null,"abstract":"<p><p>Calcific aortic valve (AV) stenosis (CAVS) is a disease associated with significant morbidity and mortality in the aging population. Recently, bile acids have been shown to play a significant role in many disease processes, and untargeted metabolomic analyses of CAVS patient valves have shown a disrupted bile acid pathway. We aimed to understand the changes in human valvular bile acids in relation to CAVS severity. A total of 100 human AVs were collected from patients undergoing AV replacement surgery. Bile acids were quantified by ultrahigh performance liquid chromatography coupled to MS/MS. Patients with mild aortic stenosis (AS) showed a distinct valvular bile acid composition compared with moderate and severe AS groups, with five bile acids being significantly elevated in patients with moderate and severe AS. These included norcholic, nordeoxycholic, glycodeoxycholic, glycocholic, and taurodeoxycholic acid. When classified by calcification score, five species were significantly different between mild and severe AS groups; four bile acids were similar when stratified based on AS severity. Using K-means clustering, we were able to distinguish valve severity by their bile acid composition. Grouping bile acids by conjugation and by primary versus secondary revealed that conjugated primary and secondary bile acids were significantly increased in stenotic valves compared with the mild AS group. Conjugated bile acids are significantly elevated in the valvular tissue of patients with severe calcific AS. These findings suggest a potential link between liver and gut microbiome physiology and bile acid pathways in contributing to the pathophysiology of valvular stenosis.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100830"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The bioactive sphingolipid playbook. A primer for the uninitiated as well as sphingolipidologists.","authors":"Yusuf A Hannun, Alfred H Merrill, Chiara Luberto","doi":"10.1016/j.jlr.2025.100813","DOIUrl":"10.1016/j.jlr.2025.100813","url":null,"abstract":"<p><p>Sphingolipids and glycosphingolipids are among the most structurally diverse and complex compounds in the mammalian metabolome. They are well known to play important roles in biological architecture, cell-cell communication, and cellular regulation, and for many biological processes, multiple sphingolipids are involved. Thus, it is not surprising that untargeted genetic/transcriptomic/pharmacologic/metabolomic screens have uncovered changes in sphingolipids and sphingolipid genes/proteins while studying physiological and pathological processes. Consequently, with increasing frequency, both targeted and untargeted mass spectrometry methodologies are being used to conduct sphingolipidomic analyses. Interpretation of such large data sets and design of follow-up experiments can be daunting for investigators with limited expertise with sphingolipids (and sometimes even for someone well-versed in sphingolipidology). Therefore, this review gives an overview of essential elements of sphingolipid structure and analysis, metabolism, functions, and roles in disease and discusses some of the items to consider when interpreting lipidomics data and designing follow-up investigations.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100813"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LDL regulates intestinal stem cell homeostasis via PPAR pathway.","authors":"Ruicheng Shi, Wei Lu, Zhiming Zhao, Bo Wang","doi":"10.1016/j.jlr.2025.100826","DOIUrl":"10.1016/j.jlr.2025.100826","url":null,"abstract":"<p><p>Epidemiological studies have highlighted a strong association between hyperlipidemia and an increased risk of cancer in the gut. Intestinal stem cells (ISCs) have been demonstrated as the cells of origin for tumorigenesis in the gut. However, the impact of hyperlipidemia on ISC homeostasis remains unclear. Here, we show that hyperlipidemia induced by LDL receptor (Ldlr) deficiency enhances ISC proliferation in vivo. Additionally, LDL treatment impairs organoid survival but increases ISC stemness ex vivo, as evidenced by the formation of poorly differentiated spheroid and higher ISC self-renewal capacity. Mechanistically, LDL treatment activates PPAR pathways, and pharmacological inhibition of PPAR and its downstream targets, including CPT1A and PDK4, mitigates the effect of LDL on ISCs. These findings demonstrate that hyperlipidemia modulates ISC homeostasis, providing new insights into the mechanism linking hyperlipidemia with tumorigenesis in the gut.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100826"},"PeriodicalIF":4.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipoprotein (a) integrates monocyte-mediated thrombosis and inflammation in atherosclerotic cardiovascular disease.","authors":"Robert S Rosenson, Ashley M Tate, Olga G Grushko, Dilna Damodaran, Qinzhong Chen, Michael Boffa, Marlys Koschinsky, Jagat Narula, Sascha N Goonewardena","doi":"10.1016/j.jlr.2025.100820","DOIUrl":"10.1016/j.jlr.2025.100820","url":null,"abstract":"<p><p>Elevated levels of lipoprotein (a) [Lp(a)], an apolipoprotein B particle, are causally linked to atherosclerotic cardiovascular disease (ASCVD). Lp(a) is thought to promote ASCVD through multiple mechanisms, including its effects on cholesterol transport, inflammation, and thrombosis. This study defines the mechanisms that integrate Lp(a)-mediated cholesterol accumulation, inflammation, and thrombosis. In this study, we employed systems biology approaches, including proteomics, transcriptomics, and mass cytometry, to define the immune cellular and molecular phenotypes in patients with ASCVD having high and low Lp(a) levels and the molecular mechanisms through which Lp(a) mediates monocyte-driven inflammation and thrombosis. In 64 stable patients with ASCVD (41 with high Lp(a) [median Lp(a) 228.7 nmol/L] and 23 with low Lp(a) [median Lp(a) 17.8 nmol/L]), we found that circulating markers of inflammation (CCL28, IL-17D) and vascular dysfunction (tissue factor [TF]; 6.4 vs. 5.7 normalized protein expression (NPX); P = 0.01) were elevated in patients with high Lp(a) levels compared with those with low Lp(a) levels. Although total monocyte and hsCRP levels were similar between the groups, CD14+ monocytes from patients with ASCVD having an elevated Lp(a) were primed and expressed more TF at baseline and in response to stress. Mechanistically, we found that Lp(a) itself can activate monocytes through Toll-like receptor 2 (TLR2) and nuclear factor kappa B (NFκB) signaling, driving both the induction of TF and TF activity. Overall, these studies are the first to link Lp(a) to monocyte-mediated inflammation and thrombosis. This study demonstrates a novel mechanism through TLR2, NFκB, and monocyte TF by which Lp(a) amplifies immunothrombotic risk.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100820"},"PeriodicalIF":4.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Drosophila estrogen-related receptor promotes triglyceride storage within the larval fat body.","authors":"Tess D Fasteen, Melody R Hernandez, Robert A Policastro, Maria C Sterrett, Gabriel E Zenter, Jason M Tennessen","doi":"10.1016/j.jlr.2025.100815","DOIUrl":"10.1016/j.jlr.2025.100815","url":null,"abstract":"<p><p>The estrogen-related receptor (ERR) family of nuclear receptors serves key roles in coordinating triglyceride (TAG) accumulation with juvenile growth and development. In both insects and mammals, ERR activity promotes TAG storage during the postembryonic growth phase, with loss-of-function mutations in mouse Esrra and Drosophila melanogaster dERR inducing a lean phenotype. However, the role of insect ERRs in controlling TAG accumulation within adipose tissue remains poorly understood, as nearly all transcriptomic and metabolomic studies have relied on whole animal analyses. Here, we address this shortcoming by using tissue-specific approaches to examine the role of dERR in regulating lipid metabolism within the Drosophila larval fat body. We find that dERR autonomously promotes TAG accumulation within fat body cells and regulates expression of genes involved in glycolysis, β-oxidation, and isoprenoid metabolism. As an extension of these results, we not only discovered that dERR mutant fat bodies exhibit decreased expression of known dHNF4 target genes but also found that dHNF4 activity is decreased in dERR mutants. Overall, our findings indicate that dERR plays a multifaceted role in the larval fat body to coordinate lipid storage with carbohydrate metabolism and developmental growth.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100815"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12155637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peroxisomal ether-glycerophospholipid synthesis is dysregulated after TBI.","authors":"Amir A Mehrabani-Tabari, Nivedita Hegdekar, Sabrina Bustos, Yulemni Morel, Yuanyuan Ji, Sazia Arefin Kachi, Olivia Pettyjohn-Robin, Sagarina Thapa, Maya Bhattiprolu, Marta M Lipinski, Jace W Jones, Chinmoy Sarkar","doi":"10.1016/j.jlr.2025.100821","DOIUrl":"10.1016/j.jlr.2025.100821","url":null,"abstract":"<p><p>Ether-glycerophospholipids (ether-GPs), the ether bond- (- O -) containing glycerophospholipids, are major components of the brain lipidome. Ether-GPs play a crucial role in regulating neuronal function, and their deficiency has been implicated in many neurodegenerative diseases. However, how they are affected after traumatic brain injury (TBI) is not known. Our data demonstrate a significant decrease in ether-GPs abundance in the mouse cortex following controlled cortical impact (CCI)-induced TBI. This is at least in part due to the impairment of peroxisomal ether-GP synthesis in the mouse brain after TBI. We detected dysregulation of peroxisomal ether-GPs synthesizing enzymes - glyceronephosphate-O-acyltransferase (GNPAT) and alkylglycerone phosphate synthase (AGPS) in the injured mouse brains. Our data demonstrate a significant decline in GNPAT level in the peroxisomal fraction and a marked accumulation of AGPS in the cytosol of mouse cortices after TBI. To restore the ether-GP level in the injured brain, we treated TBI mice with an ether-GP precursor, 1-O-octadecylglycerol (OAG), to bypass the peroxisomal ether-GPs synthesizing steps. OAG partially restored the levels of several ether-GPs, attenuated inflammatory cytokine expression, and improved their functional recovery after TBI. Taken together, our data demonstrate that the decline in ether-GPs abundance after TBI is at least in part due to the impairment in peroxisomal ether-GPs synthesis and that restoration of ether-GPs by OAG treatment can improve TBI outcomes.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100821"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating lipidome underpins gender differences in the pathogenesis of type 2 diabetes.","authors":"Madhusmita Rout, Oliver Fiehn, Dharambir K Sanghera","doi":"10.1016/j.jlr.2025.100816","DOIUrl":"10.1016/j.jlr.2025.100816","url":null,"abstract":"<p><p>Metabolic alterations in human lipidome significantly impact various chronic diseases including type 2 diabetes (T2D). However, epidemiology and clinical studies have yet to identify clinically meaningful lipid markers for T2D. Fatty acids (FAs) are the backbone of lipid species. However, conflicting results on the essential FAs including omega 3 and omega 6 in the development of metabolic diseases urge deeper evaluations of diverse clinical cohorts including underrepresented populations. This study investigated the lipidomics profiles of 3,000 individuals from a well-characterized cohort of Asian Indians. Untargeted lipidomic profiles were created using blood samples applying reversed-phase liquid chromatography-accurate mass tandem mass spectrometry. Free FAs and lysophosphatidylcholines (LPCs) were upregulated, while sphingomyelin and phosphatidylcholines were decreased in T2D. We observed a significant increase of essential FAs-FA20:4 (AA), FA20:5 (EPA), and FA22:6 (DHA) in T2D after adjusting for age, gender, and body mass index. However, most ω-3 and ω-6 FAs were reduced by 2 to 6-fold in obesity in both genders. We also observed gender differences in age-associated lipid patterns in which cholesterol sulfate and LPC 22:6 were elevated in all age groups in men, but LPC 22:6 rapidly increased after menopause in women, and sphingomyelins increased in men after 40 years. Machine learning analysis identified long-chain FAs, ether-based LPCs, and clinical risk scores among the most informative features associated with T2D. Our study identified lipidomic markers that could be potential mediators of T2D and obesity. Their patterns may underpin gender differences in the pathogenesis of metabolic and cardiovascular diseases.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100816"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12155659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}