Journal of Lipid Research最新文献

{"title":"Cyclodextrins inhibit TRPV1 and TRPA1 activation-induced nociception via cholesterol depletion.","authors":"Andrea Nehr-Majoros, Lajos Karakai, Maja Payrits, Noémi Bencze, Ágnes Kemény, György Sétáló, Rita Börzsei, Csaba Hetényi, Zsuzsanna Helyes, Éva Szőke","doi":"10.1016/j.jlr.2025.100844","DOIUrl":"10.1016/j.jlr.2025.100844","url":null,"abstract":"<p><p>The nociceptive Transient Receptor Potential Vanilloid 1 (TRPV1) and Ankyrin 1 (TRPA1) channels are predominantly expressed on peptidergic sensory nerves, being involved in pain sensation and neurogenic inflammation induced by local release of pro-inflammatory neuropeptides in the innervation area. Their activation is facilitated by cholesterol-rich lipid microdomains (lipid rafts) in the plasma membrane. Cyclodextrin (CD) derivatives deplete cholesterol from membrane rafts, reducing receptor activation in vitro, anticipating in vivo analgesic effects. We compared three different CD derivatives selected based on our previous results: random methylated β-cyclodextrin, (2-hydroxypropyl)-β-cyclodextrin and sulfobutylether-β-cyclodextrin. The effects of the topical CD pretreatments were evaluated in acute pain and neurogenic vasodilatation models in mice 30 min after TRPV1 (resiniferatoxin) or TRPA1 (formalin or mustard oil) receptor agonist administration. Intraplantar CD pretreatments significantly reduced the duration of nocifensive behaviors during the neurogenic inflammatory phase of the formalin test, as well as mechanical, but not thermal hyperalgesia following resiniferatoxin injection. CD-pretreatment significantly reduced mustard oil-induced acute neurogenic vasodilatation in the mouse ear and decreased the total cholesterol content in the plantar skin and ear tissues. Cholesterol depletion was restored by cholesterol loaded CDs. However, overloading cells with cholesterol did not significantly affect cholesterol depletion. In silico modeling showed that the methylated derivative RAMEB has different cholesterol binding mode compared to HPBCD and SBECD. We present the first in vivo results showing that these CD derivatives are promising agents for exerting peripheral analgesia and anti-inflammation via cholesterol depletion, also supported by our in vitro and in silico findings.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100844"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325987","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":"Nanodisc single-molecule pulldown to study lipid-protein interactions.","authors":"Adriana Reyes-Ordoñez, Shweta Shree, Nilmani Singh, Stephen G Sligar, Jie Chen","doi":"10.1016/j.jlr.2025.100846","DOIUrl":"10.1016/j.jlr.2025.100846","url":null,"abstract":"<p><p>Beyond serving structural roles in the cell membrane, many phospholipids, including phosphatidylinositol phosphates (PIPs), are key signaling molecules that regulate a myriad of cellular processes. Specific interactions with PIPs are crucial for the functions of many signaling proteins, highlighting the need for a convenient and robust method to study lipid-protein interactions. Previously, we established a fluorescence microscopy-based lipid single-molecule pulldown (lipid-SiMPull) assay for detecting interactions between fluorescently tagged proteins of interest in whole-cell lysates and small unilamellar vesicles containing phospholipids of interest. Despite unique advantages of the lipid-SiMPull assay, small unilamellar vesicle is not an optimal membrane model due to its instability, heterogeneity in size, and a membrane curvature inconsistent with the relative flatness of the cell membrane. Here, we report the use of lipid Nanodiscs in lipid-SiMPull. Using PIP-protein pairs of known interactions, we show that Nanodiscs containing various PIPs can pull down protein targets specifically, with an estimated detection threshold of K_d in the 10-20 μM range. Remarkably, we find that each Nanodisc is bound by one copy of the protein (or protein dimer), conferring true single-molecule resolution to the assay. Transient interactions are characterized by the rebinding of proteins to individual Nanodiscs, and dissociation rates (k_off) are determined from dwell time analysis. We apply this assay to interrogate structural requirements for the stability of AKT binding of PI(3,4,5)P₃ and find that an intramolecular interaction between the PH domain and kinase domain is critical for stabilizing the AKT-PI(3,4,5)P₃ interaction. This work estalishes the Nanodisc SiMPull assay as a simple and powerful approach for investigating protein-lipid interactions with single-molecule resolution.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100846"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368982","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":"Specific FAHFAs predict worsening glucose tolerance in non-diabetic relatives of people with Type 2 diabetes.","authors":"Ismail Syed, Ken Sluis, Pratik Aryal, Zachary Solomon, Rucha Patel, Srihari Konduri, Dionicio Siegel, Ulf Smith, Barbara B Kahn","doi":"10.1016/j.jlr.2025.100819","DOIUrl":"10.1016/j.jlr.2025.100819","url":null,"abstract":"<p><p>There is a growing need for early biomarkers for Type 2 diabetes (T2D). Fatty-Acid-Hydroxy-Fatty-Acids (FAHFAs) are bioactive lipids with >580 regioisomers in human tissues. FAHFAs such as Palmitic Acid Hydroxy Stearic Acids (PAHSAs) are anti-diabetic and anti-inflammatory. PAHSA concentrations in human serum and adipose tissue strongly correlate with insulin sensitivity. Since PAHSAs and palmitic acid hydroxy oleic acids (PAHOAs) are among the most abundant FAHFAs in human serum, we investigated whether they predict worsening glucose tolerance in first-degree relatives of people with T2D. All participants had normal glucose tolerance (NGT) at baseline; 27 remained NGT (NGT-NGT) and 21 developed impaired glucose tolerance (NGT-IGT). In NGT-NGT, total PAHSA and PAHSA regioisomer concentrations were unchanged from baseline to follow-up, while in NGT-IGT participants, most PAHSA regioisomers decreased. The initial total PAHSAs, 5-PAHSA, and 9-PAHSA, and changes in these correlated inversely with worsening glucose tolerance. Low total PAHSA concentrations at baseline and the decrease in total PAHSAs, 5-PAHSAs, and 9-PAHSAs over time predicted IGT independent of initial BMI or %body fat, change in BMI or in %body fat, initial fasting glucose, fasting insulin, or triglyceride/HDL ratio. In contrast, baseline and follow-up total PAHOA and PAHOA regioisomer levels were higher in NGT-IGT than NGT-NGT, and some PAHOA regioisomers increased during follow-up in NGT-IGT. Higher initial total PAHOAs predicted IGT independent of the same clinical variables. Thus, lower serum PAHSAs and higher PAHOAs predict worsening glucose tolerance/IGT independent of BMI, %body fat, or change in these parameters, even in lean, relatively young people.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100819"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988311","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":"Targeting to high density lipoprotein cholesterol: new insights for inflammatory bowel disease treatment.","authors":"Xiaotong Wang, Xuefei Li, Kezhen Liu, Ke Yi, Yang Yang, Dongwen Wu, Xiaowei Liu","doi":"10.1016/j.jlr.2025.100836","DOIUrl":"10.1016/j.jlr.2025.100836","url":null,"abstract":"<p><p>The anti-inflammatory and vasoprotective properties of HDL-C make it best known in cardiovascular disease and sepsis. We aimed to investigate whether interventions that target HDL-C metabolism may be used for the prevention and treatment of inflammatory bowel disease (IBD). The relationship between serum lipids and IBD clinical manifestations were analyzed in both respective and prospective cohort. Later, therapeutic effect and mechanism of cholesteryl ester transfer protein inhibitors (CETPis) in IBD treatment were explored by in vivo experiments. IBD patients had significantly reduced HDL-C, which was negatively correlated with their inflammatory status. Furthermore, HDL-C level was elevated by biologics agents and HDL-C concentration pretreatment was predictive for IBD patients' future disease severity. Elevating HDL-C by CETPi before or even after the onset of experimental colitis reduced disease severity, which is associated with an ATF3-dependent anti-inflammatory reprogramming of macrophages and with enhanced gut barrier function. Together, these results demonstrate an important role of HDL-C in IBD and indicate the potential pharmacological effects of CETPi for future IBD therapy through elevation of HDL-C.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100836"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248198","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 membrane aminophospholipids contribute to thrombotic risk in rheumatoid arthritis.","authors":"Daniela O Costa, Majd B Protty, Victoria J Tyrrell, Ali A Hajeyah, Bethan H Morgan, Ben Mead, Martin Giera, Peter W Collins, P Vince Jenkins, Ernest Choy, Simon A Jones, Valerie B O'Donnell","doi":"10.1016/j.jlr.2025.100842","DOIUrl":"10.1016/j.jlr.2025.100842","url":null,"abstract":"<p><p>Patients with rheumatoid arthritis (RA) are at elevated risk of thrombotic events, yet the underlying mechanisms remain unknown. The contribution of the procoagulant membrane surface provided by aminophospholipids (aPLs) in driving thrombotic risk in RA has not been investigated. Specifically, neither the type of aPL exposed on circulating blood cell membranes in patients is characterized nor is their ability to support thrombin generation is known. Here, lipidomics was used to characterize the external-facing and total levels of aPL molecular species in RA, specifically phosphatidylserine and phosphatidylethanolamine on extracellular vesicles (EVs), platelets, and white blood cells (WBCs). The ability of the cells and EVs to support thrombin generation from patients and healthy controls was compared using an in vitro prothrombinase assay. RA patient plasma had significantly higher levels of thrombin-antithrombin and d-dimers, indicating increased thrombotic activity in vivo. Higher EV and platelet counts were seen in RA, but WBC counts were not elevated. EVs from RA patients supported higher levels of thrombin generation compared with healthy controls, whereas for platelets and WBC, thrombin generation was similar for both groups. EVs from RA patients also showed elevated external-facing phosphatidylserine molecular species, with total aPL also increased. For platelets and WBC, total and external-facing aPL levels were similar. Thrombin-antithrombin (TAT) complexes significantly correlated with EV particle counts, indicating that their circulating numbers are directly related to coagulation in vivo. Overall, our data suggest that elevated plasma EV levels in RA are a major source of procoagulant membranes, contributing to thrombotic risk in RA.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100842"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310022","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":"Deep sphingolipidomic and metabolomic analyses of ceramide synthase 2 null mice reveal complex pathway-specific effects.","authors":"Jeongah Oh, Sneha Muralidharan, Qing Zhao, Johannes Scholz, Iris D Zelnik, Shani Blumenreich, Tammar Joseph, Tamir Dingjan, Pradeep Narayanaswamy, Hyungwon Choi, Heiko Hayen, Federico Torta, Anthony H Futerman","doi":"10.1016/j.jlr.2025.100832","DOIUrl":"10.1016/j.jlr.2025.100832","url":null,"abstract":"<p><p>The sphingolipidome contains thousands of structurally distinct sphingolipid (SL) species. This enormous diversity is generated by the combination of different long-chain bases (LCBs), N-acyl chains and head groups. In mammals, LCBs are N-acylated with different fatty acids (from C14 to C32, with different degrees of saturation) by six ceramide synthases (CerS1-6) to generate dihydroceramides (DHCer), with each CerS exhibiting specificity toward acyl-Coenzyme As of defined chain length. CerS2 synthesizes very-long chain dihydroceramide, and mice in which CerS2 has been deleted display a number of pathologies. We now expand previous analyses of the mouse sphingolipidome by examining 259 individual SL species in 18 different tissues, building an extensive SL tissue atlas of WT and CerS2 null mice. Although many of the changes in SL levels were similar to those reported earlier, a number of unexpected findings in CerS2 null mouse tissues were observed, such as the decrease in ceramide 1-phosphate levels in the brain, the increase in C26-SL levels in the lung, and no changes in levels of ceramides containing t18:0-LCBs (phytosphinganine). Furthermore, analysis of levels of other metabolites revealed changes in at least six major metabolic pathways, including some that impinge upon the SL metabolism. Together, these data highlight the complex changes that occur in the lipidome and metabolome upon depletion of CerS2, indicating how sphingolipids are connected to many other pathways and that care must be taken when assigning a relationship between tissue pathology and one or other specific SL species.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100832"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191908","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":"Liver-specific Nr1h4 deletion in mice with human-like bile acid composition causes severe liver injury.","authors":"Yusuke Mishima, Kota Tsuruya, Kinuyo Ida, Satsuki Ieda, Yutaka Inagaki, Akira Honda, Tatehiro Kagawa, Akihide Kamiya","doi":"10.1016/j.jlr.2025.100839","DOIUrl":"10.1016/j.jlr.2025.100839","url":null,"abstract":"<p><p>The farnesoid X receptor, encoded by NR1H4, is crucial for bile acid, lipid, and glucose metabolism. NR1H4 mutations in humans cause a severe liver injury called progressive familial intrahepatic cholestasis 5. However, Nr1h4 deletion in mice did not cause severe liver damage at a young age, likely because of the higher levels of hydrophilic bile acids synthesized by the mouse-specific bile acid metabolic enzymes Cyp2a12 and Cyp2c70. We aimed to assess hepatic NR1H4 function by taking advantage of the recently established Cyp2a12/Cyp2c70 double-knockout (CYPDKO) mouse model, which has a human-like bile acid composition containing mainly hydrophobic bile acids. Liver-specific Nr1h4-deficient CYPDKO mice were established using an adeno-associated virus-derived genome-editing method. Nr1h4-deficient wild-type (WT) mice showed no significant changes in marker levels for serum liver injury. In contrast, Nr1h4-deficient CYPDKO mice showed an increase in the liver/body weight ratio and serum liver injury markers, suggesting that the combination of human-like bile acid composition and Nr1h4 deletion induces liver injury. Nr1h4 deletion increased total bile acid levels in the liver through the upregulation of bile acid metabolic genes and downregulation of bile acid transporters. Conversely, overexpression of a small heterodimer partner (Shp), a downstream gene of Nr1h4, suppresses liver injury induced by Nr1h4 deletion in CYPDKO mice. Overall, liver-specific Nr1h4 deficiency induced significant liver damage in mice with human-like bile acids, unlike in WT mice, validating its use as a new animal model for cholestatic liver disease. Therefore, Shp may be a potential target for the treatment of cholestasis.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100839"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275129","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":"Elevation of hepatic de novo lipogenesis in mice with overnutrition is dependent on multiple substrates.","authors":"Jordan W Strober, Stephan Siebel, Susan F Murray, Manuel González Rodríguez, Carlos Rodriguez-Navas Gonzalez, Daniel F Vatner","doi":"10.1016/j.jlr.2025.100838","DOIUrl":"10.1016/j.jlr.2025.100838","url":null,"abstract":"<p><p>Increased de novo lipogenesis (DNL) contributes to hyperlipidemia, MASLD, and ASCVD in insulin-resistant subjects. However, multiple pathways support lipogenesis and few have sought to quantify the contributions of the discrete metabolic pathways that contribute to lipogenesis. In this study, antisense oligonucleotides (ASOs) targeting glucokinase (Gck), lactate dehydrogenase A (Ldha), and glutamic-pyruvic transaminase 2 (Gpt2) were utilized to restrict substrate flux from lipogenic precursors in C57BL6/J mice, comparing controls (CO) and chronic overnutrition (ON). In CO mice, ASO treatments did not significantly alter lipogenesis; however, there was a trend toward decreased hepatic triglyceride content and DNL, especially with the GPT2 ASO (TG = -46.8%; DNL = -53.7%). Expectedly, increased hepatic TG content and DNL (ON vs. CO: TG = +187.9%; DNL = +41.8%) were observed in mice with chronic overnutrition. Gas chromatography-mass spectrometry analyses demonstrated increased hepatic TCA cycle metabolites (ON vs. CO: fumarate +74.2%; malate +54.0%; and citrate +43.2) and decreased hepatic concentrations of multiple amino acids (ON vs. CO: Leu -41.7%; Ile -45.0%; Val -56.3%; Ser -22.6%). With ON, TG content and DNL were reduced by restricting lipogenic carbon entry from alanine (GPT2: TG = -45.5%; DNL = -48.1%), lactate (LDHA: TG = -25.8%; DNL = -33.1%), or glucose (GCK: TG = -59.2%; DNL = -69.2%). Amino acids appear to be a consistent carbon source for DNL in mice; however, carbon entry from all sources is required to maintain the significantly elevated rates of hepatic DNL in chronically overfed mice. These findings may inform the development of novel therapies and underscore the importance of peripheral substrate storage and oxidation in the prevention of dyslipidemia in the metabolic syndrome.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100838"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275128","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":"Substrate-dependent incorporation of 15-lipoxygenase products in glycerophospholipids: 15-HETE and 15-HEPE in PI, 17-HDHA in plasmalogen PE, and 13-HODE in PC.","authors":"Laura Carpanedo, Luca M Wende, Bjarne Goebel, Ann-Kathrin Häfner, Michel André Chromik, Nadja Kampschulte, Dieter Steinhilber, Nils Helge Schebb","doi":"10.1016/j.jlr.2025.100841","DOIUrl":"10.1016/j.jlr.2025.100841","url":null,"abstract":"<p><p>Several oxylipins including hydroxy-PUFAs act as lipid mediators. In biological samples, the major part occurs esterified in glycero-phospholipids (PLs) or other lipids. In this work, the incorporation into glycero-PLs of 15-hydroxyeicosatetraenoic acid (15(S)-HETE), 15(S)-hydroxyeicosapentaenoic acid (15(S)-HEPE), 17(S)-hydroxydocosahexaenoic acid (17(S)-HDHA), and 13-(S)-hydroxyoctadecadienoic acid (13(S)-HODE) was investigated in oxylipin-supplemented human embryonic kidney 293T cells and cells overexpressing 15-lipoxgenase-2 (15-LOX-2, ALOX15B). Indirect quantification of esterified oxylipins in lipid fractions showed that >97% of each supplemented 15-LOX-2 product is esterified and that <25% are bound to neutral lipids, whereas >75% are bound to distinct glycero-PL classes, depending on the hydroxy-PUFA. 15-HETE and 15-HEPE were found in phosphatidylinositol (PI)/phosphatidylserine, whereas 17-HDHA was in phosphatidylethanolamine (PE) and 13-HODE in phosphatidylcholine (PC). The same pattern was found for oxylipins endogenously formed by overexpression of 15-LOX-2. A new targeted method for the analysis of oxidized glycero-PLs enabled to pinpoint the specific molecular species of the oxylipins. 15-HETE (20:4;15OH) and 15-HEPE (20:5;15OH) are dominantly found as PI 18:0/20:4;15OH (70%) and PI 18:0/20:5;15OH (80%), respectively. This preferential incorporation of 20:4;15OH and 20:5;15OH into PI may be biologically relevant for PI signaling pathways. In contrast, >50% of 17-HDHA (22:6;17OH) was found in PE P-16:0/22:6;17OH, PE P-18:0/22:6;17OH, and PE P-18:1/22:6;17OH. At least 40% of 13-HODE (18:2;13OH) was incorporated into PC 16:0/18:2;13OH, and relevant amounts were found in PI 18:0/18;13OH, PC 18:1/18;13OH, and PC-O (ether PC) 16:0/18;13OH. These results indicate that hydroxy-PUFAs are bound to glycero-PLs in a specific manner. The distinct incorporation of 15-LOX-2 products from different PUFAs into glycero-PLs might contribute to the biological effect of these oxylipins and their precursor FAs.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100841"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310023","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":"Modeling the postprandial CETP-mediated lipid redistribution between chylomicrons, LDL and HDL.","authors":"Martin Jansen, Christine Contini, Michael M Hoffmann, Gerhard Puetz","doi":"10.1016/j.jlr.2025.100847","DOIUrl":"10.1016/j.jlr.2025.100847","url":null,"abstract":"<p><p>Impaired triglyceride (TG) metabolism is associated with metabolic diseases. Non-steady state dynamics make studying postprandial lipid metabolism challenging. We already introduced a mathematical model to estimate cholesteryl ester transfer protein (CETP)-mediated TG net flux in the fasting state. Here, we expand this model to chylomicrons (CMs) and the dynamics of postprandial lipemia. Blood samples of normolipidemic, hypertriglyceridemic, and hyperchylomicronemic volunteers were drawn at fasting and postprandial state. We separated lipoprotein classes via classical sequential ultracentrifugation. To address CMs, we developed a novel method based on Airfuge® ultracentrifugation. We studied postprandial changes of lipoproteins and their components. CETP-mediated TG redistribution was modeled based on the surface and composition data of respective lipoprotein fractions and validated by corresponding measured values. Our model estimated CETP-mediated TG flux in the fasting and postprandial state with high accuracy. Even in the postprandial condition, TG net flux to LDL/HDL is dominated by VLDL. Separating CM from VLDL and modeling both fractions instead of just using the combined CM + VLDL fraction did only improve the model's accuracy slightly (by less than 7%). The proportion of ApoC3 redistributed from HDL to VLDL in postprandial lipemia is highly correlated with the change of ApoA1 in HDL2b. Our basic model is able to estimate TG redistribution via CETP among lipoproteins in postprandial lipemia of healthy and hypertriglyceridemic subjects. An additional separation of VLDL and CM is not strictly necessary to model postprandial TG flux. Our model makes postprandial lipoprotein metabolism more tangible and may help to study lipoprotein-associated pathologies.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100847"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497348","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}