Biochimica et biophysica acta. Molecular and cell biology of lipids最新文献

{"title":"A fish intestinal in vitro model for investigation of lipid metabolism and steatosis","authors":"Daphne Siciliani ,&nbsp;Bente Ruyter ,&nbsp;Guro Løkka ,&nbsp;Kirsti Elisabeth Præsteng ,&nbsp;Matteo Minghetti ,&nbsp;Trond M. Kortner","doi":"10.1016/j.bbalip.2024.159573","DOIUrl":"10.1016/j.bbalip.2024.159573","url":null,"abstract":"<div><div>Choline is now recognized as an essential nutrient to ensure lipid transport in Atlantic salmon. Its deficiency leads to excessive lipid accumulation in the enterocytes, a condition known as steatosis. The knowledge of lipid metabolism and steatosis in fish remains limited, motivating the use of in vitro intestinal models to perform deeper explorations. This study aimed to create an in vitro steatosis model using RTdi-MI, a new cell line derived from the distal intestine of rainbow trout. Cells were exposed to varying oleic acid (OA) concentrations over different time points (24 h, 72 h, and 168 h). Results indicated that the increasing OA concentration enhanced intracellular lipid droplet formation. Quantitative lipid analysis confirmed OA accumulation, which intensified with prolonged exposure and increased OA dose. Moreover, all cells, including controls, exhibited fatty acid metabolic activity. Such outcome was confirmed by light and fluorescence microscopy. Additionally, RTdi-MI cells expressed genes involved in lipid metabolism and synthesis similar to in vivo conditions. Collectively, our findings demonstrate the ability of RTdi-MI cells to accumulate OA in intracellular lipid droplets and mirror in vivo steatosis conditions, offering a new tool for exploring fish intestinal lipid metabolism.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159573"},"PeriodicalIF":3.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hesperitin prevents non-alcoholic steatohepatitis by modulating mitochondrial dynamics and mitophagy via the AMPKα-Drp1/PINK1-Parkin signaling pathway","authors":"Suwen Chen ,&nbsp;Haifei Lu ,&nbsp;Guoliang Yin ,&nbsp;Xin Zhang ,&nbsp;Decheng Meng ,&nbsp;Wenfei Yu ,&nbsp;Linya Wang ,&nbsp;Hongshuai Liu ,&nbsp;Fengxia Zhang","doi":"10.1016/j.bbalip.2024.159570","DOIUrl":"10.1016/j.bbalip.2024.159570","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) is becoming a global public health burden, yet effective therapeutic strategies are notably lacking. NAFLD development may be mediated by mitochondrial dysfunction, according to new research. Producing mitochondrial regulators from plant-based substances to treat mitochondrial dysfunction is an appealing approach to treating NAFLD. Hesperetin (HES) is a flavonoid that is found naturally and is a member of the flavanone family. This study aims to clarify the mechanism of HES in preventing NAFLD which is caused by a high-fat diet (HFD). Serum and liver biochemical parameters, liver histology, lipid profiles, and mitochondrial function were evaluated in HFD-induced NAFLD Sprague-Dawley (SD) rats. HES treatment significantly reduced body weight gain, liver weight, and the liver index, while also improving hepatic steatosis, lipid metabolism disorders, and mitochondrial dysfunction in rats with NAFLD. The mechanism was investigated and confirmed using western blot and real-time quantitative polymerase chain reaction (RT-qPCR). We showed that in the liver of NAFLD rats, HES decreased the expression of dynamic-related protein 1 (Drp1), phosphorylated Drp1 at serine-616 (Drp1-pS616) and induced phosphorylated Drp1 at serine-637 (Drp1-pS637), PTEN-induced kinase 1 (PINK1), and E3 Ubiquitin-Protein Ligase Parkin (Parkin) via an AMP-activated protein kinase alpha (AMPKα)-dependent mechanism. Moreover, HES increased the expression of the mitochondrial fusion proteins mitofusin-2 (Mfn2) and optic atrophy 1 (Opa1) while suppressing the expression of fission protein 1 (Fis1). In this work, we identify a unique mechanism by which HES prevents NAFLD from developing. HES may be an attractive potential therapeutic agent to cure NAFLD.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159570"},"PeriodicalIF":3.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-dependent changes in visceral adiposity are associated with decreased plasma levels of DHEA-S in sigma-1 receptor knockout male mice","authors":"Gundega Stelfa ,&nbsp;Anna Miteniece ,&nbsp;Baiba Svalbe ,&nbsp;Edijs Vavers ,&nbsp;Marina Makrecka-Kuka ,&nbsp;Einars Kupats ,&nbsp;Liga Kunrade ,&nbsp;Vadims Parfejevs ,&nbsp;Una Riekstina ,&nbsp;Maija Dambrova ,&nbsp;Liga Zvejniece","doi":"10.1016/j.bbalip.2024.159571","DOIUrl":"10.1016/j.bbalip.2024.159571","url":null,"abstract":"<div><div>The sigma-1 receptor (S1R) is involved in intracellular lipid synthesis and transport. Recent studies have shown that its genetic inactivation impairs adipogenic differentiation in vitro. This study investigated the role of S1R in adipose tissue physiology and metabolic health using adult and old WT and S1R KO mice.</div><div>Visceral fat mass was increased in adult, but not old S1R-KO male mice compared to that of WT mice, despite having similar body weights, food intake, and energy expenditure. The average adipocyte size was 64 % larger in adult KO mice than in adult WT mice. Adult S1R-KO mice showed reduced plasma dehydroepiandrosterone sulfate (DHEA-S) and elevated fasting plasma leptin concentrations. Lipidomic analysis revealed alterations in plasma metabolite concentrations, particularly reduced levels of sphingomyelins, ceramides, phosphatidylcholines, lysophosphatidylcholines, and cholesteryl esters in adult mice. Decreased expression of <em>Pparγ</em>, <em>Adipoq</em>, and <em>Atgl</em> was detected in visceral white adipose tissue (vWAT) isolated from adult KO mice. Additionally, <em>Fabp4</em> and <em>Adipoq</em> expression levels were significantly lower in KO adipose-derived stromal cells than in WT adipose-derived stromal cells. A fivefold increase in the mitochondrial fatty acid oxidation rate and a 43 % increase in electron transfer coupling capacity were detected in adult S1R-KO vWAT.</div><div>In summary, our investigation revealed an age-dependent association between increased visceral adiposity and decreased plasma levels of DHEA-S in S1R-deficient male mice. These findings underscore the potential role of S1R in regulating metabolic processes in adipose tissue and suggest that DHEA-S is a potential mediator of adiposity changes in the absence of S1R.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159571"},"PeriodicalIF":3.9,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of two Plasmodium falciparum lipid transfer proteins of the Sec14/CRAL-TRIO family","authors":"Dominik Šťastný ,&nbsp;Alena Balleková ,&nbsp;Dana Tahotná ,&nbsp;Lucia Pokorná ,&nbsp;Roman Holič ,&nbsp;Jana Humpolíčková ,&nbsp;Peter Griač","doi":"10.1016/j.bbalip.2024.159572","DOIUrl":"10.1016/j.bbalip.2024.159572","url":null,"abstract":"<div><div>Invasion of human red blood cells by the malaria parasite <em>Plasmodium falciparum</em> is followed by dramatic modifications of erythrocytes properties, including <em>de novo</em> formation of new membrane systems. Lipid transfer proteins from both the parasite and the host cell are most likely an important part of those membrane remodeling processes. Using bioinformatics and <em>in silico</em> structural analysis, we have identified five <em>P. falciparum</em> potential lipid transfer proteins containing cellular retinaldehyde binding – triple functional domain (CRAL-TRIO). Two of these proteins, <span><span>C6KTD4</span><svg><path></path></svg></span>, encoded by the PF3D7_0629900 gene and <span><span>Q8II87</span><svg><path></path></svg></span>, encoded by the PF3D7_1127600 gene, were studied in more detail. <em>In vitro</em> lipid transfer assays using recombinant <span><span>C6KTD4</span><svg><path></path></svg></span> and <span><span>Q8II87</span><svg><path></path></svg></span> confirmed that these proteins are indeed <em>bona fide</em> lipid transfer proteins. <span><span>C6KTD4</span><svg><path></path></svg></span> transfers sterols, phosphatidylinositol 4,5 bisphosphate, and, to some degree, also phosphatidylcholine between two membrane compartments. <span><span>Q8II87</span><svg><path></path></svg></span> possesses phosphatidylserine transfer activity <em>in vitro</em>. In the yeast model, the expression of <em>P. falciparum</em> <span><span>Q8II87</span><svg><path></path></svg></span> protein partially complements the absence of Sec14p and its closest homologue, Sfh1p. <span><span>C6KTD4</span><svg><path></path></svg></span> protein can substitute for the collective essential function of oxysterol-binding related proteins. According to published whole genome studies in <em>P. falciparum</em>, absence of <span><span>C6KTD4</span><svg><path></path></svg></span> and <span><span>Q8II87</span><svg><path></path></svg></span> proteins has severe consequences for parasite viability. Therefore, CRAL-TRIO lipid transfer proteins of <em>P. falciparum</em> are potential targets of novel antimalarials, in search for which the yeast model expressing these proteins could be a valuable tool.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159572"},"PeriodicalIF":3.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eicosanoid biosynthesizing enzymes in Prototheria","authors":"Kumar R. Kakularam ,&nbsp;Eda Gündem ,&nbsp;Sabine Stehling ,&nbsp;Michael Rothe ,&nbsp;Dagmar Heydeck ,&nbsp;Hartmut Kuhn","doi":"10.1016/j.bbalip.2024.159569","DOIUrl":"10.1016/j.bbalip.2024.159569","url":null,"abstract":"<div><div>Eicosanoids and related compounds are pleiotropic lipid mediators, which play a role in cell differentiation and in the pathogenesis of various diseases. The biosynthesis of these lipids has extensively been studied in highly developed mammals including humans but little is known about the formation of these mediators in more ancient <em>Prototheria</em>.</div><div>We searched the genomes of two extant prototherian species (platypus, short-beaked echidna) for genes encoding for lipoxygenase- (ALOX) and prostaglandin synthase-isoforms (PTGS) and detected intact single copy genes for ALOX5, ALOX12, ALOX12B, ALOXE3, PTGS1 and PTGS2. Moreover, we identified two copies of ALOX15B genes (ALOX15B-1 and ALOX15B-2) but in echidna the ALOX15B-2 gene was structurally corrupted. Interestingly, in the two genomes ALOX15 genes were lacking. For functional characterization we expressed the prototherian ALOX15B isoforms and compared important enzyme characteristics of the wildtype proteins and of relevant enzyme mutants with those of human and mouse ALOX15B. Here we observed that the prototherian ALOX15B isoforms exhibit the same reaction specificity as their human ortholog. Mutagenesis of the Triad determinants did not alter the reaction specificity of the prototherian enzymes but modification of the Jisaka determinants murinized the catalytic properties.</div><div>These data indicate that <em>Prototheria</em> exhibit an active eicosanoid metabolism. They express functional ALOX15B orthologs but lack ALOX15 genes. These observations and the previous findings that ALOX15 orthologs rarely occur in non-mammalian vertebrates such as fish and birds suggest that ALOX15 orthologs were introduced during <em>Prototheria</em>–<em>Metatheria</em> transition via an ALOX15B gene duplication and subsequent divergent enzyme evolution.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159569"},"PeriodicalIF":3.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid imaging mass spectrometry: Towards a new molecular histology","authors":"Ibai Calvo ,&nbsp;Olatz Fresnedo ,&nbsp;Lorena Mosteiro ,&nbsp;José I. López ,&nbsp;Gorka Larrinaga ,&nbsp;José A. Fernández","doi":"10.1016/j.bbalip.2024.159568","DOIUrl":"10.1016/j.bbalip.2024.159568","url":null,"abstract":"<div><div>Lipid research is attracting greater attention, as these molecules are key components to understand cell metabolism and the connection between genotype and phenotype. The study of lipids has also been fueled by the development of new and powerful technologies, able to identify an increasing number of species in a single run and at decreasing concentrations. One of such key developments has been the image techniques that enable the visualization of lipid distribution over a tissue with cell resolution. Thanks to the spatial information reported by such techniques, it is possible to associate a lipidome trait to individual cells, in fixed metabolic stages, which greatly facilitates understanding the metabolic changes associated to diverse pathological conditions, such as cancer. Furthermore, the image of lipids is becoming a kind of new molecular histology that has great chances to make an impact in the diagnostic units of the hospitals. Here, we examine the current state of the technology and analyze what the next steps to bring it into the diagnosis units should be. To illustrate the potential and challenges of this technology, we present a case study on clear cell renal cell carcinoma, a good model for analyzing malignant tumors due to their significant cellular and molecular heterogeneity.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159568"},"PeriodicalIF":3.9,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific response of the human plasma lipidome to short-term cold exposure","authors":"Marcus Höring ,&nbsp;Sarah Brunner ,&nbsp;Josef Scheiber ,&nbsp;Julius Honecker ,&nbsp;Gerhard Liebisch ,&nbsp;Claudine Seeliger ,&nbsp;Laura Schinhammer ,&nbsp;Melina Claussnitzer ,&nbsp;Ralph Burkhardt ,&nbsp;Hans Hauner ,&nbsp;Josef Ecker","doi":"10.1016/j.bbalip.2024.159567","DOIUrl":"10.1016/j.bbalip.2024.159567","url":null,"abstract":"<div><div>Cold-induced lipolysis is widely studied as a potential therapeutic strategy to combat metabolic disease, but its effect on lipid homeostasis in humans remains largely unclear. Blood plasma comprises an enormous repertoire in lipids allowing insights into whole body lipid homeostasis. So far, reported results originate from studies carried out with small numbers of male participants. Here, the blood plasma's lipidome of 78 male and 93 female volunteers, who were exposed to cold below the shivering threshold for 2 h, was quantified by comprehensive lipidomics using high-resolution mass spectrometry. Short-term cold exposure increased the concentrations in 147 of 177 quantified circulating lipids and the response of the plasma's lipidome was sex-specific. In particular, the amounts of generated glycerophospholipid and sphingolipid species differed between the sexes. In women, the BMI could be related with the lipidome's response. A logistic regression model predicted with high sensitivity and specificity whether plasma samples were from male or female subjects based on the cold-induced response of phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and sphingomyelin (SM) species.</div><div>In summary, cold exposure promotes lipid synthesis by supplying fatty acids generated after lipolysis for all lipid classes. The plasma lipidome, i.e. PC, LPC and SM, shows a sex-specific response, indicating a different regulation of its metabolism in men and women. This supports the need for sex-specific research and avoidance of sex bias in clinical trials.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159567"},"PeriodicalIF":3.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulation of lipid metabolism in the liver of Tspo knockout mice","authors":"Fahad Farhan ,&nbsp;Rakesh Kotapati Raghupathy ,&nbsp;Michal R. Baran ,&nbsp;Aileen Wong ,&nbsp;Lincoln Biswas ,&nbsp;Hui-Rong Jiang ,&nbsp;John A. Craft ,&nbsp;Xinhua Shu","doi":"10.1016/j.bbalip.2024.159566","DOIUrl":"10.1016/j.bbalip.2024.159566","url":null,"abstract":"<div><div>The translocator protein, TSPO, has been implicated in a wide range of cellular processes exerted from its position in the outer mitochondrial membrane from where it influences lipid metabolism and mitochondrial oxidative activity. Understanding how this protein regulates a profusion of processes requires further elucidation and to that end we have examined lipid metabolism and used an RNAseq strategy to compare transcript abundance in wildtype and <em>Tspo</em> knockout (KO) mouse liver. The levels of cholesterol, triglyceride and phospholipid were significantly elevated in the KO mouse liver. The expression of cholesterol homeostasis genes was markedly downregulated. Determination of the differential expression revealed that many genes were either up- or downregulated in the KO animals. However, a striking observation within the results was a decrease of transcripts for protein degradation proteins in KO animals while protease inhibitors were enriched. When the entire abundance data-set was analysed with CEMiTool, and revealed a module of proteins that were under-represented in the KO animals. These could subsequently be formed into a network comprising three interlinked clusters at the centre of which were proteins of cytoplasmic ribosomes with gene ontology terms suggesting impairment to translation. The largest cluster was dominated by proteins of lipid metabolism but also contained disparate systems of iron metabolism and behaviour. The third cluster was dominated by proteins of the electron transport chain and oxidative phosphorylation. These findings suggest that TSPO contributes to lipid metabolism, detoxification of active oxygen species and oxidative phosphorylation, and regulates mitochondrial retrograde signalling.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159566"},"PeriodicalIF":3.9,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seasonal and genetic effects on lipid profiles of juvenile Atlantic salmon","authors":"Andrew H. House ,&nbsp;Paul V. Debes ,&nbsp;Minna Holopainen ,&nbsp;Reijo Käkelä ,&nbsp;Iikki Donner ,&nbsp;Morgane Frapin ,&nbsp;Ehsan Pashay Ahi ,&nbsp;Johanna Kurko ,&nbsp;Hanna Ruhanen ,&nbsp;Craig R. Primmer","doi":"10.1016/j.bbalip.2024.159565","DOIUrl":"10.1016/j.bbalip.2024.159565","url":null,"abstract":"<div><div>Seasonality can influence many physiological traits requiring optimal energetic capacity for life-history stage transitions. In Atlantic salmon, high-energy status is essential for the initiation of maturation. Earlier studies have linked a genomic region encoding <em>vgll3</em> to maturation age, potentially mediated via body condition. <em>Vgll3</em> has also been shown to act as an inhibitor of adipogenesis in mice. Here we investigate the influence of season and <em>vgll3</em> genotypes associating with early (EE) and late (LL) maturation on lipid profiles in the muscle and liver of juvenile Atlantic salmon. We reared Atlantic salmon for two years from fertilization and sampled muscle and liver during the spring and autumn of the second year (at which time some males were sexually mature). We found no seasonal or genotype effect in the muscle lipid profiles of immature males or females. However, in the liver we detected a triacylglycerol enrichment and a genotype specific direction of change in membrane lipids, phosphatidylcholine and phosphatidylethanolamine, from spring to autumn. Specifically, from spring to autumn membrane lipid concentrations increased in vgll3*EE individuals but decreased in vgll3*LL individuals. This could be explained by 1) a seasonally more stable capacity of endoplasmic reticulum (ER) functions in <em>vgll3</em>*EE individuals compared to <em>vgll3</em>*LL individuals or 2) <em>vgll3</em>*LL individuals storing larger lipid droplets from spring to autumn in the liver compared to <em>vgll3</em>*EE individuals at the expense of ER capacity. This genotype specific seasonal direction of change in membrane lipid concentrations provides more indirect evidence of a potential mechanism linking <em>vgll3</em> with lipid metabolism and storage.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159565"},"PeriodicalIF":3.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-evaluation of the canonical PAF pathway in cutaneous anaphylaxis","authors":"Tomoyuki Suzuki ,&nbsp;Yoshitaka Taketomi ,&nbsp;Keisuke Yanagida ,&nbsp;Tomomi Yoshida-Hashidate ,&nbsp;Takahide Nagase ,&nbsp;Makoto Murakami ,&nbsp;Takao Shimizu ,&nbsp;Hideo Shindou","doi":"10.1016/j.bbalip.2024.159563","DOIUrl":"10.1016/j.bbalip.2024.159563","url":null,"abstract":"<div><div>Platelet-activating factor (PAF) is a potent classical lipid mediator that plays a critical role in various diseases such as allergy and nervous system disorders. In the realm of allergy, previous studies suggested that PAF is generated in response to extracellular stimuli and contributes to allergic reactions <em>via</em> PAF receptor (PAFR). However, the sources of endogenous PAF and its pathophysiological dynamics remain largely elusive <em>in vivo</em>. Here, we report that rapid and local PAF generation completely depends on lysophospholipid acyltransferase 9 (LPLAT9, also known as LPCAT2) expressed in mast cells in IgE-mediated passive cutaneous anaphylaxis. However, we found that LPLAT9 knockout (KO) mice did not display attenuated vascular leakage. Additionally, decreased vascular leakage was observed in PAFR KO mice, but not in endothelial cell-specific mice in this model. These divergences highlight a yet unsolved complexity of the biological functions of PAF and PAFR in a pathophysiological process.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159563"},"PeriodicalIF":3.9,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}