Journal of Lipid Research最新文献

{"title":"SERUM AND PLASMA SPHINGOLIPIDS AS BIOMARKERS OF CHEMOTHERAPY-INDUCED CARDIOTOXICITY IN FEMALE BREAST CANCER PATIENTS.","authors":"Samia Mohammed, Andreas P Kalogeropoulos, Victoria Alvarado, Michelle Weisfelner-Bloom, Christopher J Clarke","doi":"10.1016/j.jlr.2025.100798","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100798","url":null,"abstract":"<p><p>Although effective as a chemotherapeutic, the utility of Doxorubicin (Dox) is hampered by cardiotoxicity. Despite this, the ability to predict and guide monitoring of patients receiving Dox is hampered by a lack of effective biomarkers to identify susceptible patients and detect early signs of subclinical cardiotoxicity. Based on their well-established roles in the response to Dox and other chemotherapies, we performed a retrospective analysis of serum and plasma sphingolipids (SLs) from female breast cancer (BC) patients undergoing anthracycline-containing therapy, correlating with cardiac parameters assessed by echocardiography. Results showed substantial changes in both plasma and serum SL species during therapy including ceramide (Cer), deoxydihydroCer, and dihydrosphingosine with reversion towards baseline after treatment. Linear mixed-effects model analysis revealed that baseline levels of a number of SLs correlated with adverse cardiac outcomes. Here, serum sphingosine-1-phosphate (S1P) and dihydroS1P, and plasma Cer performed comparably to the prognostic value of pro-NT-BNP, an established biomarker of cardiotoxicity. Intriguingly, while pro-NT-BNP had no predictive value at mid- and post-therapy timepoints, serum S1P and dihydroS1P and plasma Cer levels showed correlation with adverse outcomes, particularly at the post-therapy timepoint. Finally, analysis of plasma and serum C16:C24-Cer ratios - previously linked with adverse cardiac outcomes - showed no correlation in the context of chemotherapy treatment. Overall, this pilot study provides initial evidence that plasma and serum SLs may have benefit as both prognostic and diagnostic biomarkers for female BC patients undergoing anthracycline-containing chemotherapy. Consequently, diagnostic SL measurements - recently implemented for metabolic-associated cardiac disorders - could have wider utility.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100798"},"PeriodicalIF":5.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly tail-asymmetric lipids interdigitate and cause bidirectional ordering.","authors":"Tugba N Ozturk, Thomas J Ferron, Wei He, Benjamin Schwarz, Thomas M Weiss, Nicholas O Fischer, Amy Rasley, Timothy S Carpenter, Catharine M Bosio, Helgi I Ingólfsson","doi":"10.1016/j.jlr.2025.100797","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100797","url":null,"abstract":"<p><p>Phospholipids form structurally and compositionally diverse membranes. A less studied type of compositional diversity involves phospholipid tail variety. Some phospholipids contain two acyl tails which differ in length. These tail-asymmetric lipids are shown to contribute to temperature sensitivity, oxygen adaptability, and membrane fluidity. Membranes of a highly virulent intracellular bacterium, Francisella tularensis (Ft), contain highly tail-asymmetric phosphatidylethanolamine (XJPE) lipids which were previously shown to inhibit inflammatory responses in host cells. XJPE tails have unusually high asymmetry, and how they contribute to membrane properties on a molecular level is unknown. Here we use small angle X-ray scattering and molecular dynamics simulations to investigate how varying XJPE ratios alters properties of simple membranes. Our results demonstrate that at high concentration they promote liquid-to-gel transition in otherwise liquid membranes, while at low concentration they are tolerated well, minimally altering membrane properties. In liquid membranes, XJPE lipids dynamically adopt two main conformations; with the long tail extended into the opposing leaflet or bent-back residing in its own leaflet. When added to both leaflets XJPE primarily adopts an extended confirmation, while asymmetric addition results in more bent-back orientations. The former increases tail ordering and the latter decreases it. Their composition- and leaflet-dependent bidirectional effect on membrane fluidity suggests that Ft could use tail asymmetry to facilitate vesicle fusion and destabilize host cells. The effect of tail-asymmetric lipids on complex membranes should be further investigated to reveal the regulatory roles of high tail asymmetry.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100797"},"PeriodicalIF":5.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HDL Meets Triglyceride.","authors":"Tugce Akcan, Fredric B Kraemer","doi":"10.1016/j.jlr.2025.100796","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100796","url":null,"abstract":"","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100796"},"PeriodicalIF":5.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diet-induced obesity dampens the temporal oscillation of hepatic mitochondrial lipids.","authors":"Rashi Jain, Rajprabu Rajendran, Sona Rajakumari","doi":"10.1016/j.jlr.2025.100790","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100790","url":null,"abstract":"<p><p>Mitochondria play a pivotal role in energy homeostasis and regulate several metabolic pathways. The inner and outer membrane of mitochondria comprises unique lipid composition and proteins that are essential to form electron transport chain complexes, orchestrate oxidative phosphorylation, β-oxidation, ATP synthesis, etc. As known diet-induced obesity affects mitochondrial function, dynamics, and mitophagy, which are governed by circadian clock machinery. Though DIO impairs the interplay between circadian oscillation and lipid metabolism, the impact of DIO on mitochondrial membrane lipid composition and their temporal oscillation is unknown. Thus, we investigated the diurnal oscillation of liver mitochondrial lipidome at various Zeitgeber times using quantitative lipidomics. Our data suggested that obesity disrupted lipid accumulation profiles and diminished the oscillating lipid species in the hepatic mitochondria. Strikingly, HFD manifested a more homogenous temporal oscillation pattern in phospholipids regardless of possessing different fatty acyl-chain lengths and degrees of unsaturation. In particular, DIO impaired the circadian rhythmicity of phosphatidyl ethanolamine, phosphatidyl choline, phosphatidyl serine and ether-linked phosphatidyl ethanolamine. Also, DIO altered the rhythmic profile of PE/PC, ePE/PC, PS/PC ratio and key proteins related to mitochondrial function, dynamics, and quality control. Since HFD dampened lipid oscillation, we examined whether the diurnal oscillation of mitochondrial lipids synchronized with mitochondrial function. Also, our data emphasized that acrophase of mitochondrial lipids synchronized with increased oxygen consumption rate and Parkin levels at ZT16 in chow-fed mice. Our study revealed that obesity altered the mitochondrial lipid composition and hampered the rhythmicity of mitochondrial lipids, oxygen consumption rate and Parkin levels in the liver.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100790"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S-Adenosylmethionine Deficit Disrupts Very Low-Density Lipoprotein Metabolism Promoting Liver Lipid Accumulation in Mice.","authors":"María R Luque-Urbano, David Fernández-Ramos, Fernando Lopitz-Otsoa, Virginia Gutiérrez de Juan, Maider Bizkarguenaga, Lia Castro-Espadas, Uxue Hermoso-Martínez, Lucía Barbier-Torres, Shelly C Lu, Oscar Millet, José M Mato","doi":"10.1016/j.jlr.2025.100794","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100794","url":null,"abstract":"<p><p>Hepatic deletion of methionine adenosyltransferase-1a (Mat1a) in mice reduces S-adenosylmethionine (SAMe), a key methyl donor essential for many biological processes, which promotes the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Hyperglycemia and reduced MAT1A expression, along with low SAMe levels, are common in MASLD patients. This study explores how Mat1a-knockout (KO) hepatocytes respond to prolonged high glucose conditions, focusing on glucose metabolism and lipid accumulation. Hepatocytes from Mat1a-KO mice were incubated in high glucose conditions overnight, allowing for analysis of key metabolic intermediates and gene expression related to glycolysis, gluconeogenesis, glyceroneogenesis, phospholipid synthesis, and very low-density lipoprotein (VLDL) secretion. SAMe deficiency in Mat1a-KO hepatocytes led to reduced protein methyltransferase-1 activity, resulting in increased expression of glycolytic enzymes (glucokinase, phosphofructokinase, and pyruvate kinase) and decreased expression of gluconeogenic enzymes (phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase). These alterations led to a reduction in dihydroxyacetone phosphate (DHAP), which subsequently inhibited mammalian target of rapamycine complex 1 (mTORC1) activity. This inhibition resulted in decreased phosphatidylcholine synthesis via the CDP-choline pathway and impaired VLDL secretion, ultimately causing lipid accumulation. Thus, under high glucose conditions, SAMe deficiency in hepatocytes depletes DHAP, inhibits mTORC1 activity, and promotes lipid buildup.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100794"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired ApoB Secretion Triggers Enhanced Secretion of ApoE to Maintain Triglyceride Homeostasis in Hepatoma Cells.","authors":"Kotomi Shinozaki, Tomoko Honda, Kenzaburo Yamaji, Emi Nishijima, Ikuyo Ichi, Daisuke Yamane","doi":"10.1016/j.jlr.2025.100795","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100795","url":null,"abstract":"<p><p>Apolipoprotein B (ApoB) is essential for the assembly and secretion of triglyceride (TG) -rich VLDL particles, and its dysfunction is linked to metabolic disorders, including dyslipidemia and liver steatosis. However, less attention has been paid to whether and how other apolipoproteins play redundant or compensatory roles when ApoB function is compromised. Here, we investigated the effects of microsomal triglyceride transfer protein (MTP), which mediates lipidation of nascent ApoB, on ApoE function. We observed a paradoxical increase in ApoE secretion resulting from increased expression in MTP inhibitor (MTPi)-treated human hepatoma cells. This phenotype was recapitulated in APOB-knockout cells and was associated with impaired ApoB secretion. While MTP-dependent transfer of neutral lipids is dispensable for ApoE secretion, TG biosynthesis, redundantly catalyzed by DGAT1 and DGAT2, is required for efficient ApoE secretion in hepatoma cells. ApoE colocalizes with lipid droplets near the Golgi apparatus and mediates TG export in an ApoB-independent fashion. We found that simultaneous inhibition of both ApoE and ApoB, but not inhibition of either alone, led to TG accumulation in hepatoma cells, indicating that both proteins function redundantly to control TG content. Validation studies in primary human hepatocytes (PHHs) demonstrated DGAT2-dependent secretion of ApoE. While MTPi treatment did not elevate ApoE secretion, it induced increased sialylation of ApoE in the supernatants of PHHs. These results show that enhanced ApoE secretion compensates for the impaired ApoB function to maintain the lipid homeostasis, providing an alternative route to modulate lipid turnover in hepatoma cells.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100795"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms and Functional Implications of ZDHHC5 in Cellular Physiology and Disease.","authors":"Huicong Liu, Shuo Wen, Chang Xu, Xiaohong Kang, Eryan Kong","doi":"10.1016/j.jlr.2025.100793","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100793","url":null,"abstract":"<p><p>Post-translational lipid modification by palmitoylation is a reversible process crucial for maintaining cellular functionality. The palmitoyl acyltransferase zinc finger Asp-His-His-Cys motif-containing 5 (ZDHHC5) has garnered significant attention due to its roles in neurodegenerative diseases, oncogenesis, and cardiac function. ZDHHC5 recognizes substrates through diverse mechanisms and its activity is regulated by multiple factors. Highly expressed in the brain, liver and heart, ZDHHC5 exerts regulatory functions in various cellular processes through self-regulation and substrate palmitoylation. This review focuses on the regulatory roles of ZDHHC5 in the nervous system including circadian rhythm, tumor, lipid metabolism. Dysfunctions in ZDHHC5 are associated with several diseases, thereby highlighting its potential as a target for novel therapeutic strategies against neurological, lipid metabolic, and oncogenesis.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100793"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiomyopathy in a c.1528G>C Hadha Mouse is associated with Cardiac Tissue Lipotoxicity and Altered Cardiolipin Species.","authors":"Chibuike Eke, Shannon Babcock, Garen Gaston, Gabriela Elizondo, Hak Chung, Ayah Asal, Kathryn C Chatfield, Genevieve C Sparagna, Andrea E DeBarber, William Packwood, Jonathan R Lindner, Melanie B Gillingham","doi":"10.1016/j.jlr.2025.100792","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100792","url":null,"abstract":"<p><p>Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a metabolic disorder caused by the loss of LCHAD enzymatic activity in the α-subunit of the trifunctional protein (TFPα), leading to impaired fatty acid oxidation (FAO). Patients with LCHADD often develop dilated cardiomyopathy. A previously unrecognized enzymatic function of TFPα as monolysocardiolipin acyltransferase (MLCL-AT) has been implicated in cardiolipin remodeling, crucial for mitochondrial cristae integrity. However, it remains unclear whether the common pathogenic variant c.1528G>C in HADHA impairs MLCL-AT activity in TFPα. In this study, we investigated whether cardiac cardiolipin profiles are altered in LCHADD and explored potential pathophysiological mechanisms, including heart lipid accumulation, changes in the cardiolipin synthesis pathway, and mitochondrial dynamics, utilizing a murine model of LCHADD carrying c.1528G>C variant that mimics the cardiomyopathy observed in humans. LCHADD mice developed eccentric hypertrophic cardiomyopathy from 3- to 12-months of age. 12-month-old LCHADD hearts exhibited altered cardiolipin profiles and increased oxidized cardiolipin. LCHADD hearts had higher lipid content and the shift in fatty acid profile mirrored the shift in cardiolipin profile compared to wildtype controls, suggesting altered cardiolipin composition in LCHADD may be a reflection of accumulated lipids caused by lower FAO. No differential expression of cardiolipin synthesis and remodeling pathway enzymes were observed, suggesting minimal impact of the c.1528G>C variant on cardiolipin remodeling pathway. LCHADD hearts showed altered ratio of OPA1 isomers, and mitochondria with swelling and disorganized cristae were present. These findings suggest that altered fatty acid, cardiolipin profiles, and mitochondrial dynamics may contribute to LCHADD cardiomyopathy, warranting further studies.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100792"},"PeriodicalIF":5.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated High-Density Lipoprotein Triglycerides Increase Atherosclerotic Risk.","authors":"Weifang Liu, Shaoze Chen, Chengzhang Yang, Fang Lei, Xuewei Huang, Xingyuan Zhang, Tao Sun, Lijin Lin, Chuansen Wang, Yuanyuan Cao, Zhi-Gang She, Xuan Xiao, Hongliang Li","doi":"10.1016/j.jlr.2025.100791","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100791","url":null,"abstract":"<p><p>The relationship between high-density lipoprotein (HDL) and atherosclerotic risk remains incompletely elucidated, potentially due to the inherent heterogeneity of HDL particles. Hypertriglyceridemia is associated with alterations in HDL composition. This study investigated the impact of elevated triglycerides (TG) on HDL and its association with coronary artery disease (CAD) risk using a large prospective cohort study and Mendelian randomization (MR). We found that elevated TG associated with reduced HDL particle size, decreased concentrations of HDL components, and increased triglycerides in HDL (HDL-TG) (all P for trend < 0.001). The protective effects of HDL particle concentration and HDL cholesterol on CAD are attenuated with increasing serum TG levels. Independent and positive association between HDL-TG levels and incident CAD events (hazard ratio [HR] per 1 standard deviation increase: 1.066, 95% CI: 1.052-1.080, P<0.001) was confirmed even after adjustment for established cardiovascular diseases risk factors. MR analyses supported a causal role for HDL-TG in CAD development (inverse-variance weighted [IVW] method: odds ratios [ORs] of 1.120 (95% CI: 1.053-1.192, P<0.001) and 1.141 (95% CI: 1.032-1.263, P=0.010) for dataset groups 1 and 2, respectively). Drug-target MR analyses suggested a potential association between omega-3 fatty acids (OM3-FA) and lower HDL-TG levels, with LPL and DGAT2 as key pharmacological targets. Our findings suggest that elevated TG contribute to adverse alterations in HDL, elevating CAD risk. HDL-TG is an independent positive risk factor for CAD and a potential causal contributor to CAD development. OM3-FA supplementation may offer a therapeutic strategy for mitigating the CAD risk associated with elevated HDL-TG.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100791"},"PeriodicalIF":5.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isomerization of bis(monoacylglycero)phosphate by acyl migration.","authors":"Akira Abe, Vania Hinkovska-Galcheva, Rakesh Verma, James A Shayman","doi":"10.1016/j.jlr.2025.100789","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100789","url":null,"abstract":"<p><p>Bis(monoacylglycero)phosphates (BMPs) are biologically functional acidic lipids present in late endosomes and lysosomes. We recently reported that lysosomal phospholipase A2 (LPLA2, PLA2G15), the lysosomal enzyme mediating BMP catabolism, degrades BMP isomers with distinct substrate specificity. Specifically, sn-(3-Oleoyl-2-hydroxy)-glycerol-1-phospho-sn-1'-(3'-oleoyl-2'-hydroxy)-glycerol (S,S-(3,3'-diC_18:1)-BMP) is a significantly better substrate for LPLA2 than S,S-(2,2'-diC18:1)-BMP. S,S-(2,2'-diC18:1)-BMP is generally considered the only biologically relevant BMP isomer. We investigated the isomerization of S,S-(2,2'-diC_18:1)-BMP to (S,S-(3,3'-diC_18:1)-BMP) in vitro and in cells. Thin-layer chromatography was used to distinguish S,S-(3,3'-diC_18:1)-BMP from S,S-(2,2'-diC_18:1)-BMP. S,S-(2,2'-diC_18:1)-BMP/1,2-di-O-(9Z-octadecenyl)-sn-glycero-3-phosphocholine liposomes were incubated at varying pH in the presence or absence of test substances. First, we studied bovine serum albumin, which is known to promote isomerization of 1-acyl-2-lysophosphatidylcholine. The formation of S,S-(3,3'-diC_18:1)-BMP in the presence of albumin increased in a time- and albumin concentration-dependent manner under neutral conditions and was dependent on pH and the molar ratio of S,S-(2,2'-diC_18:1)-BMP in liposomes. Treatment of isomeric products generated during isomerization reaction with sn-1,3-specific lipase produced both oleic acid but also lyso-PG, indicating that the conversion of S,S-(2,2'-diC_18:1)-BMP to S,S-(3,3'-diC_18:1)-BMP is preceded via S,S-(2,3'-diC_18:1)-BMP. S,S-(3,3'-diC_18:1)-BMP formed was preferentially degraded by LPLA2 over the S,S-(2,2'-diC_18:1)-BMP. Proteins such as HSP70 and human serum albumin, and metal ions such as Fe³⁺ and Zn²⁺ acted as co-factors promoting the isomerization of S,S-(2,2'-diC_18:1)-BMP under neutral conditions. At baseline, RAW 264.7 cells showed non-negligible amounts of sn-1,3-specific lipase-sensitive BMPs. However, lipase-sensitive BMPs were increased by exposure to chloroquine or NH₄Cl, suggesting that cells undergo S,S-(2,2'-diacyl)-BMP isomerization upon alkalinization of intracellular acidic compartments.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100789"},"PeriodicalIF":5.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}