Journal of Lipid Research最新文献_第10页

Toxoplasma gondii sustains survival by regulating cholesterol biosynthesis and uptake via SREBP2 activation. 弓形虫通过 SREBP2 激活调节胆固醇的合成和吸收维持生存

IF 5 2区医学

Journal of Lipid Research Pub Date : 2024-12-01 Epub Date: 2024-10-28 DOI: 10.1016/j.jlr.2024.100684

Yi-Min Fan, Qing-Qi Zhang, Ming Pan, Zhao-Feng Hou, Lizhi Fu, Xiulong Xu, Si-Yang Huang

{"title":"Toxoplasma gondii sustains survival by regulating cholesterol biosynthesis and uptake via SREBP2 activation.","authors":"Yi-Min Fan, Qing-Qi Zhang, Ming Pan, Zhao-Feng Hou, Lizhi Fu, Xiulong Xu, Si-Yang Huang","doi":"10.1016/j.jlr.2024.100684","DOIUrl":"10.1016/j.jlr.2024.100684","url":null,"abstract":"Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that cannot biosynthesize cholesterol via the mevalonate pathway, it sources this lipid from its host. We discovered that T. gondii infection upregulated the expression of host cholesterol synthesis-related genes HMG-CoA reductase(HMGCR), squalene epoxidase (SQLE), and dehydrocholesterol reductase-7 (DHCR7), and increased the uptake pathway gene low-density lipoprotein receptor (LDLR). We found a protein, sterol regulatory element binding protein 2 (SREBP2), which is the key protein regulating the host cholesterol synthesis and uptake during T. gondii infection. T. gondii induced a dose-dependent nuclear translocation of SREBP2. Knockdown SREBP2 reduced T. gondii-induced cholesterol biosynthesis and uptake. Consequently, the parasite's ability to acquire cholesterol was significantly diminished, impairing its invasion, replication, and bradyzoites development. Interfering cholesterol metabolism using AY9944 effectively inhibited T. gondii replication. In summary, SREBP2 played an important role in T. gondii infection in vitro, serving as a potential target for regulating T. gondii-induced cholesterol metabolism, offering insights into the prevention and treatment of toxoplasmosis.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100684"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568869","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}

引用次数: 0

Differential impact of eicosapentaenoic acid and docosahexaenoic acid in an animal model of Alzheimer's disease. 二十碳五烯酸和二十二碳六烯酸对阿尔茨海默病动物模型的不同影响

IF 5 2区医学

Journal of Lipid Research Pub Date : 2024-12-01 Epub Date: 2024-10-28 DOI: 10.1016/j.jlr.2024.100682

Méryl-Farelle Oye Mintsa Mi-Mba, Meryem Lebbadi, Waël Alata, Carl Julien, Vincent Emond, Cyntia Tremblay, Samuel Fortin, Colin J Barrow, Jean-François Bilodeau, Frédéric Calon

{"title":"Differential impact of eicosapentaenoic acid and docosahexaenoic acid in an animal model of Alzheimer's disease.","authors":"Méryl-Farelle Oye Mintsa Mi-Mba, Meryem Lebbadi, Waël Alata, Carl Julien, Vincent Emond, Cyntia Tremblay, Samuel Fortin, Colin J Barrow, Jean-François Bilodeau, Frédéric Calon","doi":"10.1016/j.jlr.2024.100682","DOIUrl":"10.1016/j.jlr.2024.100682","url":null,"abstract":"Dietary supplementation with n-3 polyunsaturated fatty acids improves cognitive performance in several animal models of Alzheimer's disease (AD), an effect often associated with reduced amyloid-beta and/or tau pathologies. However, it remains unclear to what extent eicosapentaenoic (EPA) provides additional benefits compared to docosahexaenoic acid (DHA). Here, male and female 3xTg-AD mice were fed for 3 months (13-16 months of age) the following diets: (1) control (no DHA/EPA), (2) DHA (1.1g/kg) and low EPA (0.4g/kg), or (3) DHA (0.9g/kg) with high EPA (9.2g/kg). The DHA and DHA + EPA diets respectively increased DHA by 19% and 8% in the frontal cortex of 3xTg-AD mice, compared to controls. Levels of EPA, which were below the detection limit after the control diet, reached 0.14% and 0.29% of total brain fatty acids after the DHA and DHA + EPA diet, respectively. DHA and DHA + EPA diets lowered brain arachidonic acid levels and the n-6:n-3 docosapentaenoic acid ratio. Brain uptake of free 14C-DHA measured through intracarotid brain perfusion, but not of 14C-EPA, was lower in 3xTg-AD than in NonTg mice. DHA and DHA + EPA diets in 3xTg-AD mice reduced cortical soluble phosphorylated tau (pS202) (-34% high-DHA, -34% DHA + EPA, P < 0.05) while increasing p21-activated kinase (+58% and +83%, P < 0.001; respectively). High EPA intake lowered insoluble phosphorylated tau (-31% vs. DHA, P < 0.05). No diet effect on amyloid-beta levels was observed. In conclusion, dietary intake of DHA and EPA leads to differential changes in brain PUFA while altering cerebral biomarkers consistent with beneficial effects against AD-like neuropathology.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100682"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568848","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}

引用次数: 0

Prophages divert Staphylococcus aureus defenses against host lipids. 噬菌体转移了金黄色葡萄球菌对宿主脂质的防御能力。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2024-12-01 Epub Date: 2024-11-05 DOI: 10.1016/j.jlr.2024.100693

Biyang Zhou, Amit Pathania, Deepak Pant, David Halpern, Philippe Gaudu, Patrick Trieu-Cuot, Andressa Dias-Leao, Charlotte Pagot, Audrey Solgadi, Alexandra Gruss, Karine Gloux

{"title":"Prophages divert Staphylococcus aureus defenses against host lipids.","authors":"Biyang Zhou, Amit Pathania, Deepak Pant, David Halpern, Philippe Gaudu, Patrick Trieu-Cuot, Andressa Dias-Leao, Charlotte Pagot, Audrey Solgadi, Alexandra Gruss, Karine Gloux","doi":"10.1016/j.jlr.2024.100693","DOIUrl":"10.1016/j.jlr.2024.100693","url":null,"abstract":"Phages are ubiquitous in bacteria, including clinical Staphylococcus aureus, where Sfi 21/Sa3 phages often integrate into the hlb gene, which encodes Hlb sphingomyelinase. This integration acts as a rapid regulatory switch for Hlb production. Our findings suggest that Sfi 21/Sa3 prophages and Hlb activity influence S. aureus fitness by modulating the incorporation of the toxic linoleic acid (C18:2) from serum into the bacterial membrane. This process relies on C18:2 derived from 1,3-diglyceride, facilitated by the FakB1 kinase subunit. Palmitic acid (C16), primarily released from serum through Hlb activity, competes with C18:2 for FakB1. This mechanism contributes to adaptation to AFN-1252, an antibiotic inhibiting the fatty acid synthesis pathway (anti-FASII). Since S. aureus relies on exogenous fatty acids for growth, AFN-1252 treatment leads to an increased proportion of C18:2 in the membrane. Furthermore, Hlb inhibition, whether by prophage insertion, gene inactivation, or enzyme inhibition, delays S. aureus adaptation, resulting in a higher proportion of C18:2 in the membrane. This study sheds light on the role of lipid environments in infections and may contribute to the accurate prediction of infection risks and therapeutic efficacy. Moreover, since both anti-FASII agent and Hlb inhibitor enhance C18:2 incorporation, they represent potential candidates for combined strategies against S. aureus.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100693"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590914","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}

引用次数: 0

Deducing formation routes of oxylipins by quantitative multiple heart-cutting achiral-chiral 2D-LC-MS. 通过定量多重切心非手性-手性二维液相色谱-质谱联用仪推断草脂素的形成途径。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2024-12-01 Epub Date: 2024-11-05 DOI: 10.1016/j.jlr.2024.100694

Nadja Kampschulte, Rebecca Kirchhoff, Ariane Löwen, Nils Helge Schebb

{"title":"Deducing formation routes of oxylipins by quantitative multiple heart-cutting achiral-chiral 2D-LC-MS.","authors":"Nadja Kampschulte, Rebecca Kirchhoff, Ariane Löwen, Nils Helge Schebb","doi":"10.1016/j.jlr.2024.100694","DOIUrl":"10.1016/j.jlr.2024.100694","url":null,"abstract":"Several oxylipins are regulators of inflammation. They are formed by enzymes such as lipoxygenases or cyclooxygenases, but also stereorandomly by autoxidation. Reversed-phase liquid chromatography-tandem-mass-spectrometry (LC-MS/MS) methods for oxylipin quantification do not separate enantiomers. Here, we combine sensitive and selective oxylipin analysis with chiral separation using two-dimensional (2D)-LC-MS/MS. By multiple heart-cutting, the oxylipin peaks are transferred onto a chiral column. 45 enantiomeric pairs of (di-)hydroxy-fatty acids are separated with full gradient elution within 1.80 min, yielding lower limits of quantification <1 pg on the column. Concentrations, as well as enantiomeric fractions of oxylipins, can be determined, even at low concentrations or at high enantiomeric excess of one isomer. The developed achiral-chiral multiple heart-cutting 2D-LC-MS/MS method offers unprecedented selectivity, enabling a better understanding of the formation routes of these lipid mediators. This is demonstrated by distinguishing the formation of hydroxy-fatty acids by (acetylated) cyclooxygenase-2 and radical-mediated autoxidation. Applying the method to human M2-like macrophages, we show that the so-called specialized pro-resolving mediators (SPM) 5,15-DiHEPE and 7,17-DiHDHA as well as 5,15-DiHETE were present as (S,S)-enantiomers, supporting their enzymatic formation. In contrast, at least eight isomers (including protectin DX but not neutroprotectin D1) of 10,17-DiHDHA are present in immune cells, indicating formation by autoxidation. In the human plasma of healthy individuals, none of these dihydroxy-fatty acids are present. However, we demonstrate that all four isomers quickly form via autoxidation if the samples are stored improperly. Dihydroxy-FA should only be reported as SPM, such as resolvin D5 or resolvin E4, if an enantioselective analysis as described here has been carried out.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100694"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590890","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}

引用次数: 0

Effects of coconut oil, olive oil, and butter on plasma fatty acids and metabolic risk factors: a randomized trial. 椰子油、橄榄油和黄油对血浆脂肪酸和代谢风险因素的影响：随机试验。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2024-12-01 Epub Date: 2024-10-28 DOI: 10.1016/j.jlr.2024.100681

Solomon A Sowah, Albert Koulman, Stephen J Sharp, Fumiaki Imamura, Kay-Tee Khaw, Nita G Forouhi

{"title":"Effects of coconut oil, olive oil, and butter on plasma fatty acids and metabolic risk factors: a randomized trial.","authors":"Solomon A Sowah, Albert Koulman, Stephen J Sharp, Fumiaki Imamura, Kay-Tee Khaw, Nita G Forouhi","doi":"10.1016/j.jlr.2024.100681","DOIUrl":"10.1016/j.jlr.2024.100681","url":null,"abstract":"There is limited evidence on the effects of different dietary sources of fats on detailed blood fatty acids (FAs). We aimed to evaluate the effects of coconut oil, olive oil and butter on circulating FA concentrations, and examine the associations between changes in plasma FAs and changes in metabolic markers. We conducted secondary analyses in the COB (coconut oil, olive oil and butter) Trial that evaluated 96 healthy adults in a 4-week parallel randomized clinical trial of three dietary interventions: 50 g/d of extra-virgin coconut oil (n = 30), extra-virgin olive oil (n = 33), or unsalted butter (n = 33). We measured plasma phospholipid FA concentrations (mol% of total) using gas chromatography. Using linear regression, we estimated the effects of the interventions on changes in FAs and the associations of changes in selected FAs with changes in metabolic markers. Coconut oil doubled lauric acid (C12:0) and myristic acid (C14:0), butter increased those to a lesser extent, and olive oil reduced those. β (95% confidence interval) for changes in C12:0 comparing coconut oil to butter and olive oil were +0.04 (0.03-0.05) and +0.05 (0.04-0.06) mol%, respectively; for C14:0, +0.24 (0.17-0.32) and +0.37 (0.29-0.45), respectively. Olive oil increased oleic acid (OA) approximately by 1 mol%, while coconut oil and butter had little effect on OA. Butter increased odd-chain SFAs and trans-FAs while olive oil and coconut oil decreased them. Changes in FAs mostly showed no significant associations with changes in metabolic markers. The interventions of equal amounts of different food FA sources altered circulating FA concentrations differently.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100681"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568849","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}

引用次数: 0

Orm proteins control ceramide synthesis and endocytosis via LCB-mediated Ypk1 regulation. Orm 蛋白通过 LCB 介导的 Ypk1 调节来控制神经酰胺的合成和内吞。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2024-12-01 Epub Date: 2024-10-28 DOI: 10.1016/j.jlr.2024.100683

Jihui Ren, Robert Rieger, Nivea Pereira de Sa, Douglas Kelapire, Maurizio Del Poeta, Yusuf A Hannun

{"title":"Orm proteins control ceramide synthesis and endocytosis via LCB-mediated Ypk1 regulation.","authors":"Jihui Ren, Robert Rieger, Nivea Pereira de Sa, Douglas Kelapire, Maurizio Del Poeta, Yusuf A Hannun","doi":"10.1016/j.jlr.2024.100683","DOIUrl":"10.1016/j.jlr.2024.100683","url":null,"abstract":"Sphingolipids (SPLs) are major components of cell membranes with significant functions. Their production is a highly-regulated multi-step process with the formation of two major intermediates, long chain bases (LCBs) and ceramides. Homologous Orm proteins in both yeast and mammals negatively regulate LCB production by inhibiting serine palmitoyltransferase (SPT), the first enzyme in SPL de novo synthesis. Orm proteins are therefore regarded as major regulators of SPL production. Combining targeted lipidomic profiling with phenotypic analysis of yeast mutants with both ORM1 and ORM2 deleted (orm1/2Δ), we report here that Ypk1, an AGC family protein kinase, signaling is compromised in an LCB-dependent manner. In orm1/2Δ, phosphorylation of Ypk1 at its activation sites is reduced, and so is its in vivo activity shown by reduced phosphorylation of Ypk1 substrate, Lac1, the catalytic component of ceramide synthase (CerS). A corresponding defect in ceramide synthesis was detected, preventing the extra LCBs generated in orm1/2Δ from fully converting into downstream SPL products. The results suggest that Orm proteins play a complex role in regulating SPL production in yeast S. cerevisiae by exerting an extra and opposite effect on CerS. Functionally, we define endocytosis and an actin polarization defect of orm1/2Δ and demonstrate the roles of Ypk1 in mediating the effects of Orm proteins on endocytosis. Collectively, the results reveal a previously unrecognized role of yeast Orm proteins in controlling ceramide synthesis and their function in endocytosis through regulating Ypk1 signaling.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100683"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568860","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}

引用次数: 0

Humanized monoacylglycerol acyltransferase 2 mice develop metabolic dysfunction-associated steatohepatitis. 人源化单酰甘油酰基转移酶 2 小鼠患上代谢功能障碍相关性脂肪性肝炎

IF 5 2区医学

Journal of Lipid Research Pub Date : 2024-12-01 Epub Date: 2024-11-05 DOI: 10.1016/j.jlr.2024.100695

J Jose Corbalan, Pranavi Jagadeesan, Karla K Frietze, Rulaiha Taylor, Grace L Gao, Grant Gallagher, Joseph T Nickels

{"title":"Humanized monoacylglycerol acyltransferase 2 mice develop metabolic dysfunction-associated steatohepatitis.","authors":"J Jose Corbalan, Pranavi Jagadeesan, Karla K Frietze, Rulaiha Taylor, Grace L Gao, Grant Gallagher, Joseph T Nickels","doi":"10.1016/j.jlr.2024.100695","DOIUrl":"10.1016/j.jlr.2024.100695","url":null,"abstract":"Mice lacking monoacylglycerol acyltransferase 2 (mMGAT21) are resistant to diet-induced fatty liver, suggesting hMOGAT2 inhibition is a viable option for treating metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH). We generated humanized hMOGAT2 mice (HuMgat2) for use in pre-clinical studies testing the efficacy of hMOGAT2 inhibitors for treating MASLD/MASH. HuMgat2 mice developed MASH when fed a steatotic diet. Computer-aided histology revealed the presence of hepatocyte cell ballooning, immune cell infiltration, and fibrosis. Hepatocytes accumulated Mallory-Denk bodies containing phosphorylated p62/sequestosome-1-ubiquitinated protein aggregates likely caused by defects in autophagy. Metainflammation and apoptotic cell death were seen in the livers of HuMgat2 mice. Treating HuMgat2 mice with elafibranor reduced several MASH phenotypes. RNASeq analysis predicted changes in bile acid transporter expression that correlated with altered bile acid metabolism indicative of cholestasis. Our results suggest that HuMgat2 mice will serve as a pre-clinical model for testing hMOGAT2 inhibitor efficacy and toxicity and allow for the study of hMOGAT2 in the context of MASH.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100695"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590909","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}

引用次数: 0

Targeting acetyl-CoA carboxylases for the treatment of MASLD. 以乙酰-CoA 羧化酶为靶点治疗 MASLD。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2024-12-01 Epub Date: 2024-10-25 DOI: 10.1016/j.jlr.2024.100676

María Antonia Mateo-Marín, Michele Alves-Bezerra

{"title":"Targeting acetyl-CoA carboxylases for the treatment of MASLD.","authors":"María Antonia Mateo-Marín, Michele Alves-Bezerra","doi":"10.1016/j.jlr.2024.100676","DOIUrl":"10.1016/j.jlr.2024.100676","url":null,"abstract":"Hepatic accumulation of triglycerides is a hallmark feature of metabolic dysfunction-associated steatotic liver disease (MASLD). Growing evidence indicates that increased rates of de novo lipogenesis (DNL) are one of the earliest metabolic changes promoting hepatic steatosis in the onset of MASLD. The first step in DNL is catalyzed by acetyl-CoA carboxylases (ACC), which mediate the conversion of acetyl-CoA into malonyl-CoA. Given the critical role of ACC enzymes on DNL, ACC-based therapies have emerged as an attractive approach to address MASLD, leading to the development of pharmacologic inhibitors of ACC. In clinical trials, several of those compounds led to decreased DNL rates and improved hepatic steatosis in patients with MASLD. In this review, we describe the development of ACC dual inhibitors and isoform-specific inhibitors along with their clinical testing using monotherapy and combination therapy approaches. We also discuss their efficacy and safety profiles, identifying potential directions for future research. It is anticipated that advances in ACC-based therapies will be critical to the management of MASLD.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100676"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502167","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}

引用次数: 0

Diet, β-glucocerebrosidase deficiency, and Parkinson's disease. 饮食、β-葡糖脑苷脂缺乏症和帕金森病。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2024-12-01 Epub Date: 2024-10-28 DOI: 10.1016/j.jlr.2024.100689

James A Shayman

引用次数: 0

Untargeted lipidomics reveals novel HDL metabotypes and lipid-clinical correlates. 非靶向血脂组学揭示新型高密度脂蛋白代谢型和血脂临床相关性

IF 5 2区医学

Journal of Lipid Research Pub Date : 2024-12-01 Epub Date: 2024-10-25 DOI: 10.1016/j.jlr.2024.100678

Peer W F Karmaus, Scott M Gordon, Marcus Y Chen, Alison A Motsinger-Reif, Rodney W Snyder, Timothy R Fennell, Suramya Waidyanatha, Reshan A Fernando, Alan T Remaley, Michael B Fessler

{"title":"Untargeted lipidomics reveals novel HDL metabotypes and lipid-clinical correlates.","authors":"Peer W F Karmaus, Scott M Gordon, Marcus Y Chen, Alison A Motsinger-Reif, Rodney W Snyder, Timothy R Fennell, Suramya Waidyanatha, Reshan A Fernando, Alan T Remaley, Michael B Fessler","doi":"10.1016/j.jlr.2024.100678","DOIUrl":"10.1016/j.jlr.2024.100678","url":null,"abstract":"Plasma high-density lipoprotein (HDL), originally studied for its role in lipid transport, is now appreciated to have wide-ranging biological functions that become defective during disease. While >200 lipids have collectively been detected in HDL, published HDL lipidomic analyses in different diseases have commonly been targeted to prespecified subsets of lipids. Here, we report the results of untargeted lipidomic analysis of HDL isolated from 101 subjects referred for computed tomographic coronary imaging for whom multiple additional clinical and lipoprotein metadata were measured. Unsupervised clustering of the total HDL lipidome revealed that the subjects fell into one of two discrete groups, herein referred to as HDL \"metabotypes.\" Patients in metabotype 1 were likelier to be female and tended to have a less atherogenic lipoprotein profile, higher HDL cholesterol efflux capacity (CEC), and lower-grade non-calcified burden on coronary imaging than metabotype 2 counterparts. Specific lipids were relatively enriched in metabotype 1 HDL. Linear modeling revealed that several of these lipids were positively associated with CEC, statin use, HDL size, and HDL particle number, and positively correlated with HDL apolipoprotein A-1, suggesting that they may be informative HDL biomarkers. Taken together, we posit a novel, clinically relevant categorization for HDL revealed by systems biology.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100678"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568871","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}

引用次数: 0