Biochimica et biophysica acta. Molecular and cell biology of lipids最新文献_第3页

Eicosanoid biosynthesizing enzymes in Prototheria 原肠动物中的二十烷生物合成酶。

IF 3.9 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2024-10-09 DOI: 10.1016/j.bbalip.2024.159569

Kumar R. Kakularam , Eda Gündem , Sabine Stehling , Michael Rothe , Dagmar Heydeck , Hartmut Kuhn

{"title":"Eicosanoid biosynthesizing enzymes in Prototheria","authors":"Kumar R. Kakularam , Eda Gündem , Sabine Stehling , Michael Rothe , Dagmar Heydeck , 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}

引用次数: 0

Lipid imaging mass spectrometry: Towards a new molecular histology 脂质成像质谱：迈向新的分子组织学。

IF 3.9 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2024-10-05 DOI: 10.1016/j.bbalip.2024.159568

Ibai Calvo , Olatz Fresnedo , Lorena Mosteiro , José I. López , Gorka Larrinaga , José A. Fernández

{"title":"Lipid imaging mass spectrometry: Towards a new molecular histology","authors":"Ibai Calvo , Olatz Fresnedo , Lorena Mosteiro , José I. López , Gorka Larrinaga , 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}

引用次数: 0

Sex-specific response of the human plasma lipidome to short-term cold exposure 人体血浆脂质体对短期寒冷暴露的反应具有性别特异性。

IF 3.9 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2024-10-02 DOI: 10.1016/j.bbalip.2024.159567

Marcus Höring , Sarah Brunner , Josef Scheiber , Julius Honecker , Gerhard Liebisch , Claudine Seeliger , Laura Schinhammer , Melina Claussnitzer , Ralph Burkhardt , Hans Hauner , Josef Ecker

{"title":"Sex-specific response of the human plasma lipidome to short-term cold exposure","authors":"Marcus Höring , Sarah Brunner , Josef Scheiber , Julius Honecker , Gerhard Liebisch , Claudine Seeliger , Laura Schinhammer , Melina Claussnitzer , Ralph Burkhardt , Hans Hauner , 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}

引用次数: 0

Dysregulation of lipid metabolism in the liver of Tspo knockout mice Tspo 基因敲除小鼠肝脏脂质代谢失调。

IF 3.9 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2024-09-29 DOI: 10.1016/j.bbalip.2024.159566

Fahad Farhan , Rakesh Kotapati Raghupathy , Michal R. Baran , Aileen Wong , Lincoln Biswas , Hui-Rong Jiang , John A. Craft , Xinhua Shu

{"title":"Dysregulation of lipid metabolism in the liver of Tspo knockout mice","authors":"Fahad Farhan , Rakesh Kotapati Raghupathy , Michal R. Baran , Aileen Wong , Lincoln Biswas , Hui-Rong Jiang , John A. Craft , 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}

引用次数: 0

Seasonal and genetic effects on lipid profiles of juvenile Atlantic salmon 季节和遗传对大西洋鲑幼鱼脂质特征的影响。

IF 3.9 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2024-09-26 DOI: 10.1016/j.bbalip.2024.159565

Andrew H. House , Paul V. Debes , Minna Holopainen , Reijo Käkelä , Iikki Donner , Morgane Frapin , Ehsan Pashay Ahi , Johanna Kurko , Hanna Ruhanen , Craig R. Primmer

{"title":"Seasonal and genetic effects on lipid profiles of juvenile Atlantic salmon","authors":"Andrew H. House , Paul V. Debes , Minna Holopainen , Reijo Käkelä , Iikki Donner , Morgane Frapin , Ehsan Pashay Ahi , Johanna Kurko , Hanna Ruhanen , 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}

引用次数: 0

Re-evaluation of the canonical PAF pathway in cutaneous anaphylaxis 重新评估皮肤过敏性休克的典型 PAF 通路。

IF 3.9 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2024-09-25 DOI: 10.1016/j.bbalip.2024.159563

Tomoyuki Suzuki , Yoshitaka Taketomi , Keisuke Yanagida , Tomomi Yoshida-Hashidate , Takahide Nagase , Makoto Murakami , Takao Shimizu , Hideo Shindou

{"title":"Re-evaluation of the canonical PAF pathway in cutaneous anaphylaxis","authors":"Tomoyuki Suzuki , Yoshitaka Taketomi , Keisuke Yanagida , Tomomi Yoshida-Hashidate , Takahide Nagase , Makoto Murakami , Takao Shimizu , 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}

引用次数: 0

Recent advances on the physiological and pathophysiological roles of polyunsaturated fatty acids and their biosynthetic pathway 多不饱和脂肪酸的生理和病理作用及其生物合成途径的最新进展

IF 3.9 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2024-09-24 DOI: 10.1016/j.bbalip.2024.159564

Hyeon-Cheol Lee-Okada, Chengxuan Xue, Takehiko Yokomizo

{"title":"Recent advances on the physiological and pathophysiological roles of polyunsaturated fatty acids and their biosynthetic pathway","authors":"Hyeon-Cheol Lee-Okada, Chengxuan Xue, Takehiko Yokomizo","doi":"10.1016/j.bbalip.2024.159564","DOIUrl":"10.1016/j.bbalip.2024.159564","url":null,"abstract":"<div><div>Polyunsaturated fatty acids (PUFAs)—fatty acids containing multiple double bonds within their carbon chain—are an indispensable component of the cell membrane. PUFAs, including the omega-6 PUFA arachidonic acid (ARA; C20:4n-6) and the omega-3 PUFAs eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3), have been implicated in various (patho)physiological events. These PUFAs are either obtained from the diet or biosynthesized from the essential fatty acids linoleic acid (LA; C18:2n-6) and α-linolenic acid (ALA; C18:3n-3) <em>via</em> enzymatic reactions that are catalyzed by fatty acid elongases (ELOVL2 and ELOVL5) and fatty acid desaturases (FADS1 and FADS2). In this review, we summarize the recent literature studying the role of PUFAs, placing a special emphasis on the newly discovered functions of PUFAs and their biosynthetic pathway as revealed by studies using animal models targeting the PUFA biosynthetic pathway and genetic approaches including genome-wide association studies.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159564"},"PeriodicalIF":3.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324194","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}

引用次数: 0

Lipidomic and transcriptomic characteristics of boar seminal plasma extracellular vesicles associated with sperm motility 与精子活力相关的公猪精浆细胞外囊泡的脂质组和转录组特征

IF 3.9 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2024-09-02 DOI: 10.1016/j.bbalip.2024.159561

Ning Ding, Yu Zhang, Jiayao Wang, Jianfeng Liu, Jing Zhang, Chun Zhang, Lei Zhou, Jinkang Cao, Li Jiang

{"title":"Lipidomic and transcriptomic characteristics of boar seminal plasma extracellular vesicles associated with sperm motility","authors":"Ning Ding, Yu Zhang, Jiayao Wang, Jianfeng Liu, Jing Zhang, Chun Zhang, Lei Zhou, Jinkang Cao, Li Jiang","doi":"10.1016/j.bbalip.2024.159561","DOIUrl":"10.1016/j.bbalip.2024.159561","url":null,"abstract":"<div><p>Seminal plasma extracellular vesicles (SPEVs) play an important role in regulating sperm motility by delivering various cargoes, such as miRNAs, mRNAs, proteins and metabolites. However, information on the lipid compositions of SPEVs and their roles in semen quality is limited. Here, we performed high-throughput transcriptomic and lipidomic analysis on SPEVs isolated from 20 boars with high or low sperm motility. Then, we evaluated the lipid composition and gene expression characteristics of SPEVs and identified the specific lipids and genes related to sperm motility. As a result, a total of 26 lipid classes were identified in SPEVs, and five subclasses, CerG2, CerG3, LPE, LPS and TG, were significantly different in boars with high and low sperm motility. In addition, 195 important lipids and 334 important genes were identified by weighted gene coexpression analysis (WGCNA) and differential expression analysis. We observed that several important genes and lipids in SPEVs potentially influence sperm motility via glycerophospholipid metabolism, glycerolipid metabolism, the sphingolipid signaling pathway and the ferroptosis pathway. Furthermore, we found a significant correlation between the content of 22 lipids and the expression levels of 67 genes (|cor| > 0.8, <em>P</em> < 0.05). Moreover, we observed that three important gene-lipid linkages (CerG1 (d22:0/24:0) - <em>RCAN3</em>, Cer (d18:1/24:0) - <em>SCFD2</em> and CerG1 (d18:0/24:1) - <em>SCFD2</em>) were strongly correlated with sperm motility. Based on the results, some genes and lipids in SPEVs may play important roles in sperm motility by interacting with sperm through important pathways.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159561"},"PeriodicalIF":3.9,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198124001112/pdfft?md5=866d0705aaf225c6174f73f4242897f6&pid=1-s2.0-S1388198124001112-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142128993","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}

引用次数: 0

Cold-induced phosphatidylethanolamine synthesis in liver and brown adipose tissue of mice 冷诱导小鼠肝脏和棕色脂肪组织中磷脂酰乙醇胺的合成

IF 3.9 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2024-08-28 DOI: 10.1016/j.bbalip.2024.159562

Maria Soledad Hidrobo , Marcus Höring , Sarah Brunner , Gerhard Liebisch , Sabine Schweizer , Martin Klingenspor , Renate Schreiber , Rudolf Zechner , Ralph Burkhardt , Josef Ecker

{"title":"Cold-induced phosphatidylethanolamine synthesis in liver and brown adipose tissue of mice","authors":"Maria Soledad Hidrobo , Marcus Höring , Sarah Brunner , Gerhard Liebisch , Sabine Schweizer , Martin Klingenspor , Renate Schreiber , Rudolf Zechner , Ralph Burkhardt , Josef Ecker","doi":"10.1016/j.bbalip.2024.159562","DOIUrl":"10.1016/j.bbalip.2024.159562","url":null,"abstract":"<div><p>Increasing energy expenditure in brown adipose (BAT) tissue by cold-induced lipolysis is discussed as a potential strategy to counteract imbalanced lipid homeostasis caused through unhealthy lifestyle and cardiometabolic disease. Yet, it is largely unclear how liberated fatty acids (FA) are metabolized. We investigated the liver and BAT lipidome of mice housed for 1 week at thermoneutrality, 23 °C and 4 °C using quantitative mass spectrometry-based lipidomics. Housing at temperatures below thermoneutrality triggered the generation of phosphatidylethanolamine (PE) in both tissues. Particularly, the concentrations of PE containing polyunsaturated fatty acids (PUFA) in their acyl chains like PE 18:0_20:4 were increased at cold. Investigation of the plasma's FA profile using gas chromatography coupled to mass spectrometry revealed a negative correlation of PUFA with unsaturated PE in liver and BAT indicating a flux of FA from the circulation into these tissues. Beta-adrenergic stimulation elevated intracellular levels of PE 38:4 and PE 40:6 in beige wildtype adipocytes, but not in adipose triglyceride lipase (ATGL)-deficient cells. These results imply an induction of PE synthesis in liver, BAT and thermogenic adipocytes after activation of the beta-adrenergic signaling cascade.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159562"},"PeriodicalIF":3.9,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198124001124/pdfft?md5=6addaa8a37f255ac8fb4473b52a49bbf&pid=1-s2.0-S1388198124001124-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103952","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}

引用次数: 0

Spermidine mitigates ferroptosis in free fatty acid-induced AML-12 cells through the ATF4/SLC7A11/GCLM/GPX4 pathway 精胺通过 ATF4/SLC7A11/GCLM/GPX4 通路减轻游离脂肪酸诱导的 AML-12 细胞的铁变态反应

IF 3.9 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2024-08-22 DOI: 10.1016/j.bbalip.2024.159560

Jia Zhang, Tao Zhang, Yihang Chen, Xiaojie Xuan, Yuqian Zhao, Gaofeng Lu

{"title":"Spermidine mitigates ferroptosis in free fatty acid-induced AML-12 cells through the ATF4/SLC7A11/GCLM/GPX4 pathway","authors":"Jia Zhang, Tao Zhang, Yihang Chen, Xiaojie Xuan, Yuqian Zhao, Gaofeng Lu","doi":"10.1016/j.bbalip.2024.159560","DOIUrl":"10.1016/j.bbalip.2024.159560","url":null,"abstract":"<div><p>Non-alcoholic fatty liver disease (NAFLD) is a prominent cause of chronic liver disease worldwide. Spermidine (SPD), a naturally occurring polyamine, has shown potential in alleviating the accumulation of hepatic lipids and reducing NAFLD symptoms in overweight mice. Nonetheless, the specific mechanisms through which SPD exerts its effects remain largely unknown. This study seeks to explore the protective effects of SPD on NAFLD and to clarify the underlying mechanisms. An in vitro model of NAFLD was established by inducing steatosis in AML-12 cells through the use of free fatty acids (FFAs). Our experimental results demonstrate that SPD significantly reduces NAFLD development induced by FFAs. This reduction is primarily achieved through the inhibition of cellular ferroptosis, as evidenced by decreased levels of Fe<sup>2+</sup>, malondialdehyde (MDA), and reactive oxygen species (ROS). Additionally, SPD was found to enhance cellular activity and ameliorate mitochondrial dysfunction and oxidative stress caused by FFA exposure.</p><p>Further mechanistic studies have revealed that SPD upregulates the expression of solute transporter family 7a member 11 (SLC7A11), glutamate-cysteine ligase modifier subunit (GCLM), and glutathione peroxidase (GPX4). This upregulation is mediated by the activation of activating transcription factor 4 (ATF4). Knockdown experiments of ATF4 confirmed that its inhibition reverses the upregulation of SLC7A11, GCLM, and GPX4, thereby negating the protective effects of SPD. In conclusion, our findings suggest that SPD mitigates NAFLD by modulating the ATF4/SLC7A11/GCLM/GPX4 signaling pathway, resulting in the suppression of ferroptosis and the improvement of cellular health. These insights provide a novel molecular mechanism and identify potential therapeutic targets for the treatment of NAFLD.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 8","pages":"Article 159560"},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049738","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}

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