Journal of Lipid Research最新文献

{"title":"Arachidonoyl-carnitine and arachidonoyl-coenzyme A are suitable substrates for mammalian ALOX isoforms.","authors":"Xin Chen, Sahanawaz Parvez, Hannah F Wiegand, Liuhui Wu, Sabine Stehling, Astrid Borchert, Junlin Yang, Polamarasetty Aparoy, Hartmut Kuhn","doi":"10.1016/j.jlr.2025.100861","DOIUrl":"10.1016/j.jlr.2025.100861","url":null,"abstract":"<p><p>Lipoxygenases (ALOX) convert free polyenoic fatty acids to bioactive mediators, which induce phenotypic alterations in target cells. However, the intracellular concentrations of free fatty acids are very low, as these compounds are rapidly esterified with coenzyme A. The acyl-CoA esters are subsequently used for re-acylation via the Lands cycle, or they are trans-esterified to acyl carnitines for mitochondrial import. Whether acyl carnitines and acyl-CoA derivatives might also serve as ALOX substrates has not been explored. In the present study, we prepared six different wild-type mammalian ALOX-isoforms and a selected enzyme mutant, incubated the recombinant proteins in vitro with free arachidonic acid, arachidonoyl-carnitine, and arachidonoyl-coenzyme A, and quantified the amounts of primary oxygenation products. We found that for most ALOX-isoforms, arachidonoyl-carnitine was oxygenated at a similar rate as free arachidonic acid and that the chemical structures of the primary oxygenation products were identical. In contrast, arachidonoyl-coenzyme A was oxygenated with a 3-5-fold lower rate, but here again highly specific patterns of primary oxygenation products were formed. In silico docking studies and molecular dynamics simulations suggested that free arachidonic acid and arachidonoyl-carnitine are similarly aligned at the active site of rabbit ALOX15, but the binding of arachidonoyl-coenzyme A was sterically hindered because of the bulkiness of the CoA moiety. Taken together, our data indicate that acyl carnitines and fatty acid coenzyme A esters are suitable lipoxygenase substrates and that these compounds are oxygenated to isoform-specific patterns of primary oxygenation products.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100861"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667813","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":"High-density lipoprotein attenuates lipopolysaccharide-induced IL-1β activation via scavenger receptor class B type 1.","authors":"Haoyu Deng, Wan Yi Liang, Leqi Chen, Kate Huang, Rylan Mccallum, Patrick C N Rensen, John H Boyd, Mark Trinder, Liam R Brunham","doi":"10.1016/j.jlr.2025.100858","DOIUrl":"10.1016/j.jlr.2025.100858","url":null,"abstract":"<p><p>Sepsis is the dysregulated immune response to an infection and is a leading cause of mortality. Low levels of high-density lipoprotein (HDL) cholesterol are associated with increased risk of death from sepsis, and increasing levels of HDL by inhibition of cholesteryl ester transfer protein (CETP) has been shown to decrease mortality in mouse models of sepsis. The objective of this study was to investigate the cellular mechanisms by which CETP inhibition and HDL lead to improved survival during sepsis. We found that HDL inhibits lipopolysaccharide (LPS)-induced activation of IL-1β in a mouse model of sepsis. The activation of IL-1β was dependent on the activity of scavenger receptor class B type 1 (SR-B1), and knockdown of SR-B1 significantly attenuated LPS-induced production of IL-1β in macrophages. Additionally, we found that LPS-induced SR-B1 internalization occurs through the endosome-lysosome pathway, which is also likely responsible for LPS degradation in the macrophages. Furthermore, we revealed that raising HDL by CETP inhibition markedly enhanced HDL-mediated anti-inflammatory effects in response to LPS stimulation, and these effects were not due to CETP itself but rather were HDL-dependent. Finally, we show that pharmacological inhibition of CETP significantly improved endotoxemia-induced mortality by inhibiting IL-1β production in the liver and circulation after LPS injection. Pathologically, CETP inhibition attenuated LPS-induced diffuse alveolar damage and hepatocyte necrosis, which may contribute to the improved mortality in mice treated with the CETP inhibitor anacetrapib. Taken together, our findings uncover a cellular mechanism by which HDL attenuates LPS-induced pro-inflammatory response via SR-B1-mediated LPS degradation.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100858"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12345257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575660","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":"Fatty acid nitroalkenes regulate intestinal lipid absorption.","authors":"Francisco J Schopfer, Lihong Teng, Ahssan Sekandari, Ese S Ekhator, Alison B Kohan, Bruce A Freeman, Marco Fazzari","doi":"10.1016/j.jlr.2025.100855","DOIUrl":"10.1016/j.jlr.2025.100855","url":null,"abstract":"<p><p>Fatty acid nitroalkenes (NO₂-FA) are tissue-protective and anti-inflammatory endogenous lipid mediators. A unique electrophilic character promotes reversible reactions with protein thiols, influencing key cellular functions. Given their generation during digestion and therapeutic potential, understanding the mechanisms and impact of NO₂-FA absorption and distribution is crucial. We investigated the intestinal absorption of orally administered 10-nitro-octadec-9-enoic acid (10-NO₂-OA) in male and female rats, using a portal vein- and mesenteric lymph duct-cannulated conscious model. There were no sex-related differences in the plasma distribution of 10-NO₂-OA and its inactive metabolite 10-nitro-octadecanoic acid (10-NO₂-SA). 10-NO₂-OA was extensively esterified into triglycerides at concentrations ∼60 times greater than the free acid. Duodenal administration showed that 10-NO₂-OA is primarily incorporated into chylomicron triglycerides (TAG) and transported via the lymphatic system, bypassing initial hepatic metabolism. Notably, 10-NO₂-OA significantly reduced lymph flow, chylomicron secretion, and impacted the lymphatic TAG profile and transit. Assessment of intestinal TAG uptake by ³H-triolein tracing in mice showed that 10-NO₂-OA significantly reduced dietary fat absorption by 75%. Quantitation of radioactivity distribution along the gastrointestinal tract showed a trend to greater lipid incorporation into the mucosa. Overall, these results show that NO₂-FA are primarily absorbed and transported through the lymphatic system as esterified TAG species, undergoing initial metabolism in enterocytes regardless of sex, with an unexpected impact on intestinal fatty acid uptake. These findings reveal novel actions of both endogenously formed and orally administered electrophilic NO₂-FA in modulating inflammatory and metabolic syndrome-related pathologies.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100855"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567525","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":"Repurposing daclatasvir for MASLD Therapy-A promising step forward with challenges ahead.","authors":"Carlos Jose Pirola","doi":"10.1016/j.jlr.2025.100857","DOIUrl":"10.1016/j.jlr.2025.100857","url":null,"abstract":"<p><p>The article discusses the potential of repurposing daclatasvir, an FDA-approved anti-HCV drug, for treating metabolic dysfunction-associated steatotic liver disease (MASLD) and its advanced form, metabolic dysfunction-associated steatohepatitis (MASH). The study by Shu et al. identifies daclatasvir as a potent inhibitor of perilipin-2 (PLIN2), a protein central to lipid droplet stability and metabolic homeostasis. Daclatasvir enhances MARCH6-mediated ubiquitination of PLIN2, leading to its degradation, which reduces lipid accumulation, inflammation, and fibrosis-key features of MASLD and MASH. Preclinical models demonstrate its ability to improve lipid metabolism, reduce inflammation, and alleviate liver fibrosis. Despite promising findings, challenges remain. Clinical trials are needed to validate its efficacy and safety in humans, as animal models cannot fully replicate the multifactorial nature of MASLD. Long-term safety and potential off-target effects also require evaluation, especially since PLIN2 may protect against other liver conditions. The study highlights the need for broader screening of FDA-approved drugs and exploration of alternative pathways for PLIN2 regulation. While daclatasvir shows promise, further research is essential to address these gaps and advance its clinical application for MASLD therapy. The findings underscore the potential of drug repurposing as a cost-effective strategy for unmet medical needs.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100857"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567527","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":"Daytime-restricted feeding induces lean MAFLD in high-fat diet-fed mice by upregulating CD36-mediated lipid accumulation.","authors":"Zhenyu Wang, Mingyang Zhang, Miao Chen, Shuning Fu, Yang Zhang, Mengyue Chen, Xiong Z Ruan, Yaxi Chen","doi":"10.1016/j.jlr.2025.100853","DOIUrl":"10.1016/j.jlr.2025.100853","url":null,"abstract":"<p><p>Time-restricted feeding (TRF) may aid in weight loss and improve metabolic health; however, its long-term effects and applicability to all individuals remain unclear. This study investigated the impact of different dietary patterns on hepatic metabolism by subjecting mice to either a normal chow diet or a high-fat diet, allowing for ad libitum feeding, daytime restrictive feeding (DRF), or nighttime restrictive feeding (NRF). Using metabolic cages to assess energy intake, we found that the fuel utilization rhythms of DRF mice were disrupted compared to ad libitum-fed mice. Mice on normal chow DRF exhibited only dyslipidemia, while those on high-fat DRF developed lean metabolic dysfunction-associated fatty liver disease (MAFLD), characterized by more pronounced dyslipidemia, weight loss, and hepatic lipid accumulation. RNA seq revealed that CD36 plays a crucial role in the development of lean MAFLD induced by high-fat DRF by inhibiting AMPK phosphorylation, disrupting the balance between lipogenesis and oxidation. Mechanistic validation was performed in CD36 liver-specific knockout mice and Liposomal nanoparticle injection models. These findings provide new insights into the potential mechanisms linking feeding patterns to lean MAFLD. Additionally, CD36 emerges as a potential therapeutic target for high-fat-induced lean MAFLD. Clarifying the relationship between DRF and lean MAFLD may inform guidelines for specific populations, such as individuals practicing intermittent fasting or those working night shifts, while also suggesting potential therapeutic strategies for clinical management.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100853"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497337","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":"Functional characterization of genetic variants affecting the intracellular domains of ATP-binding cassette transporter A1 (ABCA1).","authors":"Marianne Teigen, Åsa Schawlann Ølnes, Katrine Bjune, Martin Prøven Bogsrud, Thea Bismo Strøm","doi":"10.1016/j.jlr.2025.100854","DOIUrl":"10.1016/j.jlr.2025.100854","url":null,"abstract":"<p><p>The ATP-binding cassette transporter A1 (ABCA1) effluxes cellular cholesterol and phospholipids to extracellular acceptors, mainly apolipoprotein A1, generating high-density lipoprotein (HDL) particles. This is the first step in the anti-atherosclerotic process of transporting excess cholesterol from non-hepatic tissues to the liver. Loss-of-function variants in ABCA1 lead to reduced HDL cholesterol levels in plasma, thus possibly diminishing the atheroprotective effect of HDL. More than 250 missense variants have been reported in the ABCA1 gene, most of which remain to be functionally characterized. In this study, we have characterized 74 variants affecting the intracellular domains of ABCA1 by assessing cholesterol efflux activity and cell surface localization of the protein, thereby shifting the pathogenicity classification of 10 variants from class 3 (uncertain significance) to class 4 (likely pathogenic) or class 2 (likely benign). Consequently, functional characterization contributes to a better understanding of the molecular basis of the pathogenicity of genetic variants in ABCA1, which could also clarify the mechanism of action of the protein.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100854"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567526","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":"Cerebrospinal fluid lipoprotein-mediated cholesterol delivery to neurons is impaired in Alzheimer's disease and involves APOE4.","authors":"Carla Borràs, Marina Canyelles, David Santos, Noemí Rotllan, Estefanía Núñez, Jesús Vázquez, Daniel Maspoch, Mary Cano-Sarabia, Qi Zhao, Maria Carmona-Iragui, Sònia Sirisi, Alberto Lleó, Juan Fortea, Daniel Alcolea, Francisco Blanco-Vaca, Joan Carles Escolà-Gil, Mireia Tondo","doi":"10.1016/j.jlr.2025.100865","DOIUrl":"10.1016/j.jlr.2025.100865","url":null,"abstract":"<p><p>In the central nervous system, apolipoprotein (APO)E-containing lipoprotein particles mediate the transport of glial-derived cholesterol to neurons, which is essential for neuronal membrane remodeling and maintenance of the myelin sheath. We aimed to examine cholesterol transport via lipoprotein particles in cerebrospinal fluid (CSF) of Alzheimer's disease (AD) patients compared to control individuals. Additionally, we explored the ability of reconstituted HDL containing different APOE isoforms to regulate cholesterol transport. We evaluated the capacity of CSF lipoprotein particles to facilitate radiolabeled unesterified cholesterol efflux from A172 human glioblastoma astrocytes and to deliver cholesterol to SH-SY5Y human neuronal cells. The CSF lipoprotein proteome was analyzed by LC-MS/MS. Reconstituted HDL nanoparticles were prepared by combining phospholipids and cholesterol with human APOE3 or APOE4, followed by radiolabeling with unesterified cholesterol. Our results showed that cholesterol efflux from astrocytes to CSF were similar between AD patients and controls, both under baseline conditions and after activation of ABCA1 and ABCG1. However, CSF lipoprotein-mediated neuronal cholesterol uptake was significantly reduced in the AD group. LC-MS/MS analysis identified 239 proteins associated with CSF lipoproteins in both groups, with no major alterations in proteins linked to cholesterol metabolism. However, 27 proteins involved in noncholesterol-related processes were differentially expressed. Notably, synthetic reconstituted HDL particles containing APOE4 exhibited reduced capacity to deliver cholesterol to neurons compared to those with APOE3. These findings indicate that CSF lipoproteins from patients with AD demonstrate impaired cholesterol delivery to neurons. Our study highlights APOE4 as a critical contributor to abnormal neuronal cholesterol uptake in AD pathophysiology.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100865"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12391596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698830","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":"Introduction of a lipidomics scoring system for data quality assessment.","authors":"Nils Hoffmann, Robert Ahrends, Erin S Baker, Kim Ekroos, Xianlin Han, Michal Holčapek, Gerhard Liebisch, Markus R Wenk, Yu Xia, Harald C Köfeler","doi":"10.1016/j.jlr.2025.100817","DOIUrl":"10.1016/j.jlr.2025.100817","url":null,"abstract":"<p><p>The scientific field of lipidomics has shown a constantly growing publication number in recent years, which is accompanied by an increasing need for quality standards. While the official shorthand nomenclature of lipids is a first and important step toward a reporting quality tool, an additional point score would reflect the quality of reported data at an even more detailed granularity. Thus, we propose a lipidomics scoring scheme that considers all the different layers of analytical information to be obtained by mass spectrometry, chromatography, and ion mobility spectrometry and awards scoring points for each of them. Furthermore, the scoring scheme is integrated with the annotation levels as proposed by the official shorthand nomenclature, with a point score, which roughly correlates with the annotated compound details. The merit of such a scoring system is the fact that it abstracts evidence for structural information into a number, which gives even the nonlipidomics expert an idea about the reporting, and by extension, data quality at first glance. Additionally, it could serve as an aid for internal quality control and for data quality assessment in the peer review process.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100817"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12345285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029829","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":"Effects of fasting on HDL particle function and size distribution.","authors":"Joanne K Agus, Angela M Zivkovic","doi":"10.1016/j.jlr.2025.100859","DOIUrl":"10.1016/j.jlr.2025.100859","url":null,"abstract":"<p><p>The effects of fasting on high-density lipoprotein (HDL) particles remain an area of ongoing investigation. This narrative review examines the impact of various fasting regimens, including intermittent fasting (IF) and continuous fasting (CF), on HDL cholesterol (HDL-C), particle size distribution, and concentration. Current evidence on fasting's influence on HDL particles is limited and inconsistent, particularly in IF studies, where variability in HDL metrics, recruitment bias, and confounding factors-such as weight loss as a primary study goal-complicate interpretation. While some CF studies suggest a mild trend toward decreased HDL-C and alterations in HDL particle size distribution, the overall health implications of these changes remain unclear. Further research is needed to provide a more comprehensive understanding of how fasting affects HDL particles and their broader implication for health and disease.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100859"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12345262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584160","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":"Non-invasive identification of steatohepatitis in patients with MASLD using a sterol and lipidomic signature.","authors":"Ratna Budhi Pebriana, Ting Chen, Rico J E Derks, Niek Blomberg, Aldo Grefhorst, Yassene Mohammed, Max Nieuwdorp, Joanne Verheij, Michail Doukas, Patrick C N Rensen, Adriaan G Holleboom, Maarten E Tushuizen, Martin Giera","doi":"10.1016/j.jlr.2025.100845","DOIUrl":"10.1016/j.jlr.2025.100845","url":null,"abstract":"<p><p>The accumulation of cholesterol and other lipids leading to hepatic lipotoxicity drives the progression of metabolic dysfunction-associated steatotic liver (MASL) to metabolic dysfunction-associated steatohepatitis (MASH), the advanced progressive stage of metabolic dysfunction-associated steatotic liver disease (MASLD). For MASH diagnosis, liver biopsy remains the reference standard, despite its invasiveness and limitations. Thus, this study aimed to find blood-derived lipid markers for MASH. We investigated serum samples from 86 patients with histologically characterized MASLD, spanning the disease spectrum (i.e. 62 patients with MASL (Fibrosis grade 0-4) and 24 patients with MASH (Fibrosis grade 2-4) with a balanced distribution of hepatocellular carcinoma) and analyzed sterol composition and lipidome. To identify the presence of MASH, logistic regression was performed on each candidate either in a single or combination with various clinical parameters. Serum levels of desmosterol and phosphatidylcholine are increased in patients with MASH compared to those with MASL. After exclusion of patients using lipid lowering drugs, an increase was also found in serum levels of cholesterol, cholesterol ester, lysophosphatidylcholine, lysophosphatidylethanolamine, phosphatidylethanolamine, and several individual lipid species. The ROC curve of each lipid candidate show the potential use of desmosterol, phosphatidylcholine, and a panel of lipid species in combination with alanine aminotransferase as potential diagnostic markers, characterized by a respective AUROC of 0.79 (95% CI 0.66-0.92), 0.80 (95% CI 0.64-0.97), and 0.91 (95% CI 0.82-1.00). Serum sterol and lipidome markers are characterized by strong AUROC results to distinguish with high accuracy MASH from MASL, potentially paving the way for future MASH biomarker development.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100845"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368983","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}