Journal of Lipid Research最新文献

{"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}

{"title":"HBV-miR-3 induces hepatic cholesterol accumulation by targeting ABCA1: Evidence for potential benefits of statin usage.","authors":"Shruti Chowdhari, Auroni Deep, Belal Ahmad, Jasmine Samal, Ekta Gupta, Perumal Vivekanandan","doi":"10.1016/j.jlr.2025.100866","DOIUrl":"10.1016/j.jlr.2025.100866","url":null,"abstract":"<p><p>The cellular targets of hepatitis B virus (HBV)-encoded miRNAs remain poorly understood. The evolutionary conservation of HBV-miR-3 across HBV genotypes suggests its potential functional importance. Transcriptome profiling of HBV-miR-3 expressing hepatocytes demonstrates differential expression of several genes associated with lipid metabolic processes. The cholesterol efflux regulator gene ABCA1 was found to be downregulated in our microarray data and GEO datasets from HBV-infected liver. We validated ABCA1 as a bona fide target of HBV-miR-3. HBV-miR-3-mediated suppression of ABCA1 led to increased cholesterol and lipid droplet accumulation in addition to increased proliferation and colony formation in hepatocyte cell lines. Interestingly, widely prescribed cholesterol-lowering drugs (simvastatin, atorvastatin, and fluvastatin) could inhibit the pro-oncogenic effects of HBV-miR-3. HBV-miR-3 expression was detectable in all liver biopsies (n = 20) from patients with chronic HBV (CHBV). Patients with high intrahepatic HBV loads had higher levels of HBV-miR-3, suggesting that the virus-encoded miRNA levels correlate with virus replication. Patients with high HBV-miR-3 expression had significantly lower ABCA1 transcript levels in the liver. Hepatic steatosis was more frequently observed in biopsies of patients with high intrahepatic HBV-miR-3 levels compared to those with low HBV-miR-3 levels (71% vs. 53%), although this was not statistically significant. Taken together, our findings support the notion that HBV-miR-3-mediated suppression of ABCA1 contributes to dysregulation of lipid metabolism in CHBV infection. In sum, HBV-miR-3 may represent the \"missing link\" between CHBV and altered lipid metabolism in hepatocytes. Statin-mediated inhibition of HBV-miR-3-induced intrahepatic lipid accumulation and cell proliferation has potential clinical utility and merits further investigation.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100866"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12391803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698831","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":"Optogenetic perturbation of lipid droplet localization affects lipid metabolism and development in Drosophila.","authors":"Xin Deng, Wei Wang, Dandan Peng, Luhao Zhang, Zhihao Ma, Junfen Fu, Chao Tong, Yingke Xu","doi":"10.1016/j.jlr.2025.100848","DOIUrl":"10.1016/j.jlr.2025.100848","url":null,"abstract":"<p><p>Lipid droplets (LDs) are dynamic organelles crucial for lipid storage and homeostasis. Despite extensive documentation of their importance, the causal relationship between LD localization and function in health and disease remains inadequately understood. Here, we developed optogenetics-based tools, termed \"Opto-LDs,\" which facilitate the interaction between LDs and motor proteins in a light-dependent manner, enabling precise control of LD localization within cells. Utilizing these optogenetic modules, we demonstrated that light-induced relocation of LDs to the periphery of hepatocytes results in elevated very-low-density lipoprotein (VLDL) secretion, recapturing the beneficial effect of insulin in vitro. Furthermore, our studies in transgenic Drosophila revealed that proper LD localization is critical for embryonic development, with mistargeting of LDs significantly affecting egg hatching success. In summary, our work underscores the great importance of LD localization in lipid metabolism and development, and our developed tools offer valuable insights into the functions of LDs in health and disease.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100848"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368984","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":"Human hepatoma Huh-7 cell culture models deficient in apolipoprotein B secretion.","authors":"Swati Valmiki, Sara Rosario, Ashley Mooring, Chandana Prakashmurthy, Florencia Schlamp, Binu Prakash, Atrayee Chattopadhyay, Abulaish Ansari, José O Alemán, Nathalie Pamir, M Mahmood Hussain","doi":"10.1016/j.jlr.2025.100867","DOIUrl":"10.1016/j.jlr.2025.100867","url":null,"abstract":"<p><p>ApoB is an essential structural protein for the assembly and secretion of triglyceride-rich lipoproteins and therefore remains a potential target to lower plasma cholesterol levels in hypercholesterolemia patients. To understand the global consequences of APOB gene deficiency, we employed CRISPR-Cas9 system to generate apoB-deficient human hepatoma Huh-7 cells (Ako cells). ApoB was not detectable in the cells and media of the Ako cells. ApoB deficiency had no effect on microsomal triglyceride transfer protein expression and activity. These cells supported apoB48 secretion when transfected with plasmids for the expression of apoB48 suggesting that these cells retain all the lipoprotein assembly and secretion machinery except for apoB expression. APOB gene deficiency had no significant effect on cellular lipid levels, cell growth, and ER stress markers. Proteome analysis of secreted proteins revealed that the most upregulated protein was the vitamin D binding protein, while the most downregulated protein was apoB in Ako cells compared to control cells. This analysis also identified coagulation as an upregulated pathway. Total RNA transcriptome analysis identified DNA replication and complement and coagulation pathways as the most upregulated pathways in Ako cells. Further detailed studies are needed to establish how apoB regulates these pathways. These Ako cells may be useful in studying structure-function analysis of apoB peptides and to address the cellular consequences of disruptions in lipoprotein assembly and secretion.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100867"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717960","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 risk of going outside: Amino phospholipids in rheumatoid arthritis.","authors":"Nicola Pozzi, David A Ford","doi":"10.1016/j.jlr.2025.100870","DOIUrl":"10.1016/j.jlr.2025.100870","url":null,"abstract":"","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100870"},"PeriodicalIF":4.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760328","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}