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

{"title":"The interplay of transcriptional regulator SREBP1 with AMPK promotes lipid biosynthesis in Mucor circinelloides WJ11","authors":"Tahira Naz ,&nbsp;Xiang Yu Zhao ,&nbsp;Shaoqi Li ,&nbsp;Tariq Saeed ,&nbsp;Samee Ullah ,&nbsp;Yusuf Nazir ,&nbsp;Qing Liu ,&nbsp;Hassan Mohamed ,&nbsp;Yuanda Song","doi":"10.1016/j.bbalip.2024.159592","DOIUrl":"10.1016/j.bbalip.2024.159592","url":null,"abstract":"<div><div>SREBP1 is a transcription factor that influences lipogenesis by regulating key genes associated with lipid biosynthesis, while AMPK, modulates lipid metabolism by regulating acetyl-CoA carboxylase. The exact role of these metabolic regulators in oleaginous microbes remains unclear. This study identified and manipulated the genes encoding SREBP1 (<em>sre1</em>) and α1 subunit of AMPK (<em>ampk-α1</em>) in <em>Mucor circinelloides</em> WJ11. Individual overexpression of <em>sre1</em> yielded 32.5 % lipids and 21 g/L biomass, while ampk-α1 deletion combined with sre1 overexpression yielded 42.5 % lipids and 25 g/L biomass in mutant strains. This increase correlated with upregulated expression of key lipogenic genes and enzyme activity, enhancing lipid production and biomass. These surges were correlated with the increased mRNA levels of key genes (<em>acl</em>, <em>acc1</em>, <em>acc2</em>, <em>cme1</em>, <em>fas1</em>, <em>g6pdh1</em>, <em>g6pdh2 and 6pgdh2</em>)<em>.</em> Enzyme activity analysis further showed that upregulation of ACL, ACC, ME, FAS, G6PDH and 6PGDH might provide more precursors and NADPH for lipid biosynthesis in <em>sre1</em> overexpressing strains. Conversely, the activities of these genes and enzymes were markedly downregulated in <em>sre1</em> deleted mutants consistent with lower lipid production and biomass than the control. These findings open new avenues for research by exploring the coordinated role of <em>sre1</em> and <em>ampk-α1</em> in lipid metabolism in <em>M. circinelloides</em>.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159592"},"PeriodicalIF":3.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902567","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":"Loss of SUR2 alters the composition of ceramides and shortens chronological lifespan of Saccharomyces cerevisiae","authors":"Zhitao Deng,&nbsp;Qianqian Wang,&nbsp;Rongbin Ding,&nbsp;Weiwei Nie,&nbsp;Xiaoyan Chen,&nbsp;Yu Chen,&nbsp;Yanlu Wang,&nbsp;Jingjing Duan,&nbsp;Zhenying Hu","doi":"10.1016/j.bbalip.2024.159591","DOIUrl":"10.1016/j.bbalip.2024.159591","url":null,"abstract":"<div><div>Sphingolipids are crucial components of cell membranes and serve as important signaling molecules. Ceramide, as the central hub of sphingolipid metabolism, plays a significant role in various biological processes, including the cell cycle, apoptosis, and cellular aging. Alterations in sphingolipid metabolism are implicated in cellular aging, however, the specific sphingolipid components and intrinsic mechanisms that mediate this process remain largely uncharacterized. In this study, we established a targeted sphingolipidomics approach and employed LC-MS/MS to quantitatively analyze changes in ceramide levels during chronological aging and in <em>sur2</em>Δ strains, aiming to elucidate the role of ceramides in regulating chronological lifespan. Our study revealed that in <em>Saccharomyces cerevisiae</em>, the C4 hydroxylase Sur2 and its product, phytoceramide, increase during chronological aging. While the loss of <em>SUR2</em> function leads to a near-complete loss of phytoceramides and an accumulation of dihydroceramides, resulting in a significant reduction of total ceramide content to about half of that in wild-type cells. This ceramide profile alteration impairs both mitochondrial morphology and function, ultimately shortening the chronological lifespan. The knockout of <em>SIT4</em> restores mitochondrial morphology and function, and rescues the chronological lifespan of <em>SUR2</em>-deficient yeast. Our findings highlight the critical role of dihydroceramide and phytoceramide in chronological aging in yeast and suggest that an imbalance between these two metabolites may trigger downstream ceramide signaling pathways. These insights could help elucidate potential mechanisms through which ceramide imbalance contributes to disease development in higher organisms.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159591"},"PeriodicalIF":3.9,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884957","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":"Hippo pathway activation causes multiple lipid derangements in a murine model of cardiomyopathy","authors":"Wei Wu ,&nbsp;Kevin Huynh ,&nbsp;Jin-Chan Du ,&nbsp;Gang She ,&nbsp;Thy Duong ,&nbsp;Mark Ziemann ,&nbsp;Wei-Bo Zhao ,&nbsp;Xiu-Ling Deng ,&nbsp;Peter J. Meikle ,&nbsp;Xiao-Jun Du","doi":"10.1016/j.bbalip.2024.159590","DOIUrl":"10.1016/j.bbalip.2024.159590","url":null,"abstract":"<div><div>Metabolic reprogramming occurs in cardiomyopathy and heart failure contributing to progression of the disease. Activation of cardiac Hippo pathway signaling has been implicated in mediating mitochondrial dysfunction and metabolic reprogramming in cardiomyopathy, albeit influence of Hippo pathway on lipid profile is unclear. Using a dual-omics approach, we determined alterations of cardiac lipids in a mouse model of cardiomyopathy due to enhanced Hippo signaling and explored molecular mechanisms. Lipidomic profiling discovered multiple alterations in lipid classes, notably reduction of triacylglycerol, diacylglycerol, phospholipids and ether lipids, and elevation of sphingolipids and lysophosphatidylcholine. Mechanistically, we found downregulated expression of PPARα and PGC-1α at mRNA and protein levels, and downregulated expression of PPARα-target genes, indicating attenuated transcriptional activity of PPARα/PGC-1α. Lipidomics-guided transcriptomic analysis revealed dysregulated expression of gene sets that were responsible for enhanced biosynthesis of ceramides, suppression of TG biosynthesis, storage, hydrolysis and mitochondrial fatty acid oxidation, and reduction of peroxisome-localized biosynthesis of ether lipids. Collectively, Hippo pathway activation with attenuated PPARα/PGC-1α signaling is the underlying mechanism for alterations in cardiac lipids in cardiomyopathy and failing heart.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159590"},"PeriodicalIF":3.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871151","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":"Expression, purification and characterization of a dual function α-dioxygenase/peroxidase from Mycolicibacterium smegmatis","authors":"Teresa Rotolo,&nbsp;Anna Kaye,&nbsp;Lauren Fahrenkrog,&nbsp;Kate Flynn,&nbsp;Elisabeth C. Ford,&nbsp;Barry S. Selinsky","doi":"10.1016/j.bbalip.2024.159587","DOIUrl":"10.1016/j.bbalip.2024.159587","url":null,"abstract":"<div><div>An open reading frame from the actinobacterium <em>Mycolicibacterium smegmatis</em> annotated as a Prostaglandin H Synthase (PGHS) was expressed with an N-terminal (his)₆ tag and purified to homogeneity. The enzyme has a monomeric molecular weight of 68.3 kD and exists as a dimer in the presence of nonionic detergent. The enzyme uses saturated and unsaturated fatty acids as substrates and catalyzes two reactions: the addition of molecular oxygen alpha to the carboxylate group to form the 2-hydroperoxy fatty acid, followed by reduction to the 2-hydroxy fatty acid. The initial reduction reaction does not require a source of electrons, but electrons must be provided from an appropriate donor such as epinephrine for the reduction reaction to go to completion. Minor reaction products one carbon atom shorter than the original fatty acid substrate are also observed; These most likely arise from the spontaneous decarboxylation of the 2-hydroperoxy fatty acid product to form an aldehyde. This dual function dioxygenase/peroxidase is unusual among the lipid dioxygenases and may represent a bacterial precursor to mammalian PGHS.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159587"},"PeriodicalIF":3.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862772","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":"Effect of glucose selenol on hepatic lipid metabolism disorder induced by heavy metal cadmium in male rats","authors":"Xinyi Yang ,&nbsp;Jinzhou Huang ,&nbsp;Juan Wang ,&nbsp;Huimin Sun ,&nbsp;JinJin Li ,&nbsp;Shunfeng Li ,&nbsp;Yun-e Tang ,&nbsp;Zhi Wang ,&nbsp;Qisheng Song","doi":"10.1016/j.bbalip.2024.159589","DOIUrl":"10.1016/j.bbalip.2024.159589","url":null,"abstract":"<div><div>This study used 24 male rats to determine the protective effects of a new selenium molecule (glucose selenol) on cadmium (Cd) induced hepatic toxicity. The rats were randomly divided into four groups: control group, Cd group, Cd + 0.15 Se group, and Cd + 0.4 Se group. The results showed that glucose selenol supplementation alleviated the adverse impact of Cd on lipid metabolism, including decreased serum triacylglycerol and cholesterol levels. Transcriptome analysis revealed that, compared to the control group, Cd changed the expression of 1379 genes - discernibly affecting lipid metabolism pathways. Proteomic analysis primarily indicated alterations in lipid metabolism-related pathways. In conclusion, glucose selenol restored lipid metabolism disorders induced by Cd, thus rescuing hepatic damage. This integrated analysis identified the influence of glucose selenol on Cd-induced hepatic toxicity and provided its potential application prospects in alleviating the impact of heavy metal pollution, such as Cd, on human health.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159589"},"PeriodicalIF":3.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823780","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":"Effect of N-glycosylation on secretion, degradation and lipoprotein distribution of human serum amyloid A4","authors":"Toru Takarada ,&nbsp;Rikako Fujinaka ,&nbsp;Masaki Shimada ,&nbsp;Masakazu Fukuda ,&nbsp;Toshiyuki Yamada ,&nbsp;Masafumi Tanaka","doi":"10.1016/j.bbalip.2024.159588","DOIUrl":"10.1016/j.bbalip.2024.159588","url":null,"abstract":"<div><div>Serum amyloid A (SAA) is a family of apolipoproteins predominantly synthesized and secreted by the liver. Human SAA4 is constitutively expressed and contains an N-glycosylation site that is not present in other SAA subtypes. SAA4 proteins are not fully glycosylated, resulting in the presence of both glycosylated and non-glycosylated forms in human plasma. The efficiency of N-glycosylation in SAA4 is known to be influenced by some reasons such as genetic polymorphism and metabolic disorders. However, the specific role of N-glycosylation in SAA4 remains largely unexplored. This study aimed to investigate how N-glycosylation affects the secretion, degradation, and lipoprotein distribution of SAA4. Initially, we designed and constructed an SAA4 plasmid vector to compare with the expression pattern of endogenous SAA4. The exogenous SAA4 was partially N-glycosylated, analogous to endogenous SAA4 in human hepatocellular carcinoma cells. Subsequently, we created a non-glycosylated mutant by replacing asparagine 76 with glutamine. Immunoblotting assays showed that the disruption of N-glycans did not affect the secretion and degradation of SAA4. Furthermore, we analyzed the lipoprotein profiles of SAA4 in the conditioned medium derived from transfected cells. The results revealed that non-glycosylated mutant SAA4 exhibited a distinct lipoprotein distribution compared to wild-type SAA4. Our findings suggest that N-glycosylation may be a key regulator of the distribution of SAA4 in lipoproteins, shedding light on the previously unknown physiological activities of human SAA4.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159588"},"PeriodicalIF":3.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821725","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":"Origin and evolution of yeast carotenoid pathways","authors":"Gerhard Sandmann","doi":"10.1016/j.bbalip.2024.159586","DOIUrl":"10.1016/j.bbalip.2024.159586","url":null,"abstract":"<div><div>Carotenoid pathways exist in nature in all domains. Comparison of the genes involved and their distribution allowed the elucidation of the origin and evolution of carotenoid biosynthesis from an early common ancestor of prokaryotes to Bacteria and Archaea. From the latter domain, carotenogenic genes are inherited by fungi as the only phylum of Eukarya. Carotenoid biosynthesis in the algal-plant lineage emerged independently by endosymbiotic gene transfer from an engulfed carotenogenic cyanobacterium. The early set of carotenogenic genes included <em>crtB</em> of phytoene synthase, the desaturase gene <em>crtI</em>, and the lycopene cyclase gene <em>crtYcd</em> for the synthesis of β-carotene. This carotenoid is further metabolised either to zeaxanthin and retinal due to the presence of <em>crtZ</em> and <em>ccd</em> or elongated to a C₅₀ carotenoids by the <em>crtEb</em> gene product. The diversified pathways, especially in bacteria and fungi, result from gene modifications altering the substrate and product specificities of the corresponding enzymes or from the acquisition of novel genes. This was highlighted in more detail for the carotenoid pathways in the red yeasts of Basidiomycota leading to torularhodin, 2′-plectaniaxanthin, and astaxanthin.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159586"},"PeriodicalIF":3.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817105","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":"Single-cell transcriptomic analysis and luteolin treatment reveal three adipogenic genes, including Aspn, Htra1 and Efemp1","authors":"Tao Tao ,&nbsp;Yanting Xu ,&nbsp;Cheng-hui Zhang ,&nbsp;Xian Zhang ,&nbsp;Juan Chen ,&nbsp;Jian Liu","doi":"10.1016/j.bbalip.2024.159585","DOIUrl":"10.1016/j.bbalip.2024.159585","url":null,"abstract":"<div><div>A comparative transcriptomic analysis in adipose stem and progenitor cells (ASPCs) between obese and lean mice might facilitate the identification of novel adipogenic genes. Here, we compare transcriptomic differences in the ASPCs of subcutaneous adipose tissue (SAT) between the mice fed on a high-fat-diet (HFD) and the chow diet (CD)-fed mice by analyzing three independent single-cell RNA sequencing datasets. Six differential genes, including three up-regulated genes <em>Aspn</em>, <em>Rrbp1</em>, <em>Fbln2</em> and three down-regulated genes <em>Htra1</em>, <em>Plpp3</em>, <em>Efemp1</em>, are identified and confirmed in HFD-fed mice. Further, the expression of these genes is found to be significantly diminished in the differentiated 3T3-L1 cells. Treatment with luteolin, a dietary flavonoid known to inhibit 3T3-L1 adipogenesis, reverses the decreased expression of <em>Aspn</em>, <em>Htra1</em> and <em>Efemp1</em>. Furthermore, knockdown of <em>Aspn</em>, <em>Htra1</em> and <em>Efemp1</em> significantly facilitates 3T3-L1 adipogenesis. Together, these genes not only are differential in ASPCs between obese and lean mice, but also are the adipogenic inhibitory genes that can be up-regulated by luteolin treatment.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159585"},"PeriodicalIF":3.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812134","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":"The intestine-specific homeobox (ISX) modulates β-carotene-dependent regulation of microsomal triglyceride transfer protein (MTP) in a tissue-specific manner","authors":"Youn-Kyung Kim ,&nbsp;Elena Giordano ,&nbsp;Ulrich Hammerling ,&nbsp;Dhruv Champaneri ,&nbsp;Johannes von Lintig ,&nbsp;M. Mahmood Hussain ,&nbsp;Loredana Quadro","doi":"10.1016/j.bbalip.2024.159584","DOIUrl":"10.1016/j.bbalip.2024.159584","url":null,"abstract":"<div><div>Vitamin A is an essential nutrient crucial to ensuring proper mammalian embryonic development. β-Carotene is the most prevalent form of vitamin A in food that, when transferred in its intact form from mother to the developing tissues, can serve as an <em>in situ</em> source of retinoic acid, the active form of vitamin A. We have previously provided evidence that the maternal-fetal transfer of β-carotene across the placenta is mediated by lipoproteins and that β-carotene itself regulates placenta lipoprotein biogenesis by means of its derivatives β-apo-10′-carotenoids and retinoic acid. These metabolites exert antagonistic transcriptional activity on placental microsomal triglyceride transfer protein (MTP) and apolipoprotein B (APOB), two key players of lipoprotein biosynthesis. Here, we analyzed the time-dependency of this regulation over the course of 24 h upon a single maternal administration of β-carotene. We also tested the hypothesis that the transcriptional repressor intestine-specific homeobox (ISX) plays a role in the regulation of <em>Mttp</em> in placenta. We observed that ISX is expressed in placenta of mouse dams and is regulated by β-carotene availability. Furthermore, we demonstrated that the absence of <em>Isx</em> disrupts the β-carotene-mediated regulation of placental MTP. We also showed that this mechanism is organ-specific, as it was not observed in enterocytes of the intestine, a major place of <em>Isx</em> expression. Therefore, we identified ISX as a “master” regulator of a placental β-carotene-dependent transcriptional regulatory cascade that fine-tunes the flux of provitamin A carotenoid towards the developing fetus.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159584"},"PeriodicalIF":3.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790970","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":"PLAAT5 as an N-acyltransferase responsible for the generation of anti-inflammatory N-acylethanolamines in testis","authors":"Mohammad Mamun Sikder ,&nbsp;Sumire Sasaki ,&nbsp;Yoshimi Miki ,&nbsp;Yuki Nagasaki ,&nbsp;Ken-ichi Ohta ,&nbsp;Zahir Hussain ,&nbsp;Hiroyuki Saiga ,&nbsp;Mari Ohmura-Hoshino ,&nbsp;Katsuaki Hoshino ,&nbsp;Masaki Ueno ,&nbsp;Miki Okada-Iwabu ,&nbsp;Makoto Murakami ,&nbsp;Natsuo Ueda ,&nbsp;Toru Uyama","doi":"10.1016/j.bbalip.2024.159583","DOIUrl":"10.1016/j.bbalip.2024.159583","url":null,"abstract":"<div><div><em>N</em>-Acylethanolamines (NAEs) are a class of lipid mediators that exhibit anti-inflammatory and appetite-suppressive activities. Among them, palmitoylethanolamide (PEA) and arachidonoylethanolamide (AEA) bind to peroxisomal proliferator-activated receptor (PPAR) α and cannabinoid receptor CB1, respectively. <em>N</em>-Acyl-phosphatidylethanolamine (NAPE) as a precursor of NAEs is biosynthesized from membrane phospholipids by <em>N</em>-acyltransferases, which consist of group IVE cytosolic phospholipase A₂ε (cPLA₂ε) and PLAAT (phospholipase A and acyltransferase) family enzymes. While cPLA₂ε is responsible for the production of NAEs not only in specific tissues, including muscle, skin, and the stomach, but also under pathological conditions, such as psoriasis and brain ischemia, the involvement of the PLAAT family <em>in vivo</em> remains unclear. Considering the specific expression of PLAAT5 in testes, we investigated the potential role of PLAAT5 in the formation of NAEs in testes using PLAAT5-deficient (<em>Plaat5</em>^{<em>−/−</em>}) mice. High-performance liquid chromatography coupled with tandem mass spectrometry showed that PLAAT5 deficiency decreased the total level of NAEs by 61 %, with PEA and AEA being reduced by 64 % and 87 %, respectively. Following a treatment with cadmium chloride, an environmental toxin that induces testicular inflammation, the expression of inflammatory genes (<em>Il6</em>, <em>Tnf</em>, and <em>Nos2</em>) in testes was markedly higher in <em>Plaat5</em>^{<em>−/−</em>} mice than in <em>Plaat5</em>^<em>+/+</em> mice, and their expression was attenuated by the administration of PEA and AEA. Furthermore, these anti-inflammatory effects were canceled by a co-treatment with the antagonists of PPARα or CB1. These results suggest that PLAAT5 is responsible for the biosynthesis of anti-inflammatory NAEs in testes.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159583"},"PeriodicalIF":3.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725331","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}