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

{"title":"Gossypin suppresses mutant KRAS G12D driven oncogenic and adipogenic activity via NF-κB signaling in pancreatic cancer.","authors":"Jyoti Poswal, Kiran Kumar Tejavath, Vaibhav Kushwaha, R S Vidya, Hemanth Naick Banavath, Sanjay Kumar Dey, Chandi C Mandal","doi":"10.1016/j.bbalip.2026.159779","DOIUrl":"https://doi.org/10.1016/j.bbalip.2026.159779","url":null,"abstract":"<p><p>Pancreatic cancer is an aggressive malignancy driven largely by mutant KRAS and constitutively active downstream NF-κB pathway. Molecular docking of phenolic bioflavonoids identified a few lead compounds targeting KRAS G12D mutant protein. Gossypin exhibited better molecular docking, where MD simulation depicted a stable energetically favorable gossypin-KRAS complex, compared to other molecules. Isothermal titration calorimetry analysis confirmed the existence of thermodynamically favorable interaction between KRAS G12D and the ligand gossypin. Influence of gossypin on pancreatic cancer was not explored till date. This study aimed to address the role of KRAS downstream target NF-κB in mediating anti-oncogenic and lipid metabolic effects of gossypin in pancreatic cancer. Gossypin treatment significantly inhibited cell proliferation, migration, invasion, and stemness potential in pancreatic PANC-1 and MIA PaCa-2 cancer cells. This lead molecule blocked PI3K/AKT/mTOR and ERK signaling with concomitant inhibition of NF-κB activity. P65 (a subunit of NF-κB) overexpression was found to efficiently rescue the inhibitory effect of gossypin on oncogenic and adipogenic activities, including lipid accumulation, cholesterol and triacylglyceride contents in PANC-1 cells. This suppressed adipogenic potential was accompanied by downregulation of lipid regulatory genes (e.g., SREBF1, HMGCoR, and Perilipin-1) upon gossypin treatment. SREBF1 transcription was directly regulated by NF-κB as evidenced in ChIP assay. Moreover, down-regulated adipogenic potential-mediated by knocking down of SREBF1 gene was retained upon forced expression of p65, suggesting that NF-κB-stimulated lipogenic activity is dependent on SREBP1. These findings, for the first time, unravel KRAS/NF-κB/SREBP1 signaling as a central mediator for gossypin-inhibited lipid metabolic activity and subsequent oncogenic potential in pancreatic cancer.</p>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":" ","pages":"159779"},"PeriodicalIF":3.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223300","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":"LUR1 (SPRING1) promotes sortilin-induced macrophage lipid accumulation and aortic atherosclerosis via furin maturation.","authors":"Yuncheng Lv, Xiaoming Fan, Chuangbiao Lin, Huijuan Li, Yun Wang, Xiaping Jiang, Xiangyang Tang, Fang Liu","doi":"10.1016/j.bbalip.2026.159778","DOIUrl":"https://doi.org/10.1016/j.bbalip.2026.159778","url":null,"abstract":"<p><strong>Background: </strong>This study was undertaken to investigate the contributions of largely Golgi-localized proteins-lipid uptake regulator 1 (LUR1, SPRING1), the protease furin, and sortilin-in oxidized low-density lipoprotein (ox-LDL)-treated macrophages and atherosclerotic mouse models.</p><p><strong>Methods: </strong>Bioinformatics analysis was employed to predict the interaction between LUR1 and furin and their potential involvement in AS. The binding of LUR1 to furin was detected using a co-immunoprecipitation (Co-IP) assay. Gene and protein expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot in THP-1 macrophages transfected with recombinant lentiviruses. Cellular lipid content was measured by colorimetry, and lipid droplets were evaluated by Oil Red O staining. Plasma lipid profiles were measured using an enzymatic oxidation method. Histological staining was performed to investigate aortic atherosclerotic lesions in male LDLR^-/- mice fed a high-fat diet (HFD).</p><p><strong>Results: </strong>LUR1 increased the expression and maturation of macrophage sortilin. Co-IP confirmed LUR1-furin binding. The mRNA and protein levels of furin and sortilin were increased upon LUR1 OE, while the ratios of pro-furin/mature-furin and pro-sortilin/total-sortilin decreased, thereby enhancing lipid uptake in macrophages. Infection with adeno-associated virus 9 (AAV9)-LUR1 elevated plasma levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), and increased lipid deposition and AS plaque area in the vessel walls of male HFD-fed LDLR^-/- mice.</p><p><strong>Conclusion: </strong>LUR1 was implicated in furin/sortilin maturation, accelerating macrophage lipid accumulation and the progression of aortic AS.</p>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":" ","pages":"159778"},"PeriodicalIF":3.8,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219778","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":"Long non-coding RNA LINC00885 contributes to liver steatosis through modulation of DHRS2-associated lipid metabolic programs.","authors":"Kuei-Yen Tsai, Po-Li Wei, Kang-Yi Su, Cheng-Chin Lee, Uyanga Batzorig, Chien-Yu Huang, Yu-Jia Chang","doi":"10.1016/j.bbalip.2026.159777","DOIUrl":"https://doi.org/10.1016/j.bbalip.2026.159777","url":null,"abstract":"<p><strong>Background and aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent and rising liver disease. Its inflammatory subtype, metabolic dysfunction-associated steatohepatitis (MASH), can progress to fibrosis, cirrhosis, and hepatocellular carcinoma. The role of long intergenic non-protein coding RNA 885 (LINC00885) in MASLD remains unknown. This study aims to clarify its function in steatotic liver disease.</p><p><strong>Methods: </strong>Public liver transcriptomic datasets, RNA sequencing of LINC00885-knockdown Hep G2 cells, and microarray profiling under lipotoxic conditions were integrated to identify candidate downstream components. Gain- and loss-of-function models, Oil Red O staining, RT-qPCR, an actinomycin D chase assay, functional rescue, and JC-1 analysis were used to evaluate the LINC00885-DHRS2 axis. Circulating exosomal RNA and exploratory ROC analyses were assessed in a pilot cohort.</p><p><strong>Results: </strong>LINC00885 was upregulated in MASH liver tissue and induced by FFA treatment in hepatocytes. LINC00885 promoted lipid accumulation and shifted lipid metabolic gene expression toward lipogenesis. Integrated transcriptomic analyses identified DHRS2 as a convergent downstream candidate. LINC00885 knockdown increased DHRS2 expression and was associated with slower DHRS2 mRNA decay. DHRS2 exerted an anti-steatotic phenotype, and DHRS2 depletion reversed the reduction in lipid accumulation caused by LINC00885 knockdown. DHRS2 perturbation was also accompanied by changes in mitochondrial membrane potential. In a pilot serum cohort, exosomal LINC00885 and DHRS2 showed opposite expression patterns and preliminary discriminative potential.</p><p><strong>Conclusions: </strong>The findings support a functional LINC00885-DHRS2 axis associated with hepatocellular lipid accumulation, lipid metabolic gene expression, and mitochondrial membrane potential. The circulating exosomal observations are exploratory and require validation in larger, clinically characterized cohorts.</p>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":" ","pages":"159777"},"PeriodicalIF":3.8,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206426","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":"Role of lipid droplet-mediated lipid peroxidation by GPX4 in docosahexaenoic acid-induced EA.hy926 endothelial cell ferroptosis","authors":"Youjia Du ,&nbsp;Yan Shen ,&nbsp;Ruotong Wang ,&nbsp;Xiaoou Ren ,&nbsp;Shoudong Ye","doi":"10.1016/j.bbalip.2026.159748","DOIUrl":"10.1016/j.bbalip.2026.159748","url":null,"abstract":"<div><div>Endothelial cells (EC) form the inner lining of the blood vessels and are essential for the vascular homeostasis. EC death has been implicated in the pathology of vascular diseases. Our previous studies indicated that docosahexaenoic acid (DHA) induces EA.hy926 EC death by upregulating lipid droplet (LD) biogenesis and activating p38 MAPK, however, how LDs contribute to this process remains unclear. DHA belongs to the polyunsaturated fatty acids that are susceptible to lipid peroxidation, which is a common mechanism in lipid-induced cell injury and ferroptosis. Therefore, the current study is to investigate the mechanism of LD in the regulation of lipid peroxidation in relation to p38 MAPK in DHA-induced EA.hy926 endothelial ferroptosis. Results showed that DHA induced a time-dependent, bidirectional modulation of GPX4 expression accompanied by a progressive GSH and NADPH depletion and increased lipid peroxidation in ECs. Suppression of LD formation through diacylglycerol acyltransferases inhibition, siRNA, or promotion of LD lipolysis reduced lipid peroxidation and restored the GPX4 expression. Inhibiting lipid peroxidation chemically, activating GPX4 or supplementing GSH all prevented the cell death by DHA. Our findings reveal a novel role of LD in regulating GPX4-mediated lipid peroxidation and highlight the key role of p38 MAPK in downregulating GPX4 in lipid peroxidation-induced EC ferroptosis by DHA. In conclusion, the present study suggested that DHA-induced LD formation in ECs increases the membrane area, which could facilitate the lipid peroxidation reaction, disrupt the endogenous GPX4 antioxidant system, and thereby exacerbate the detrimental effects of lipid peroxidation, ultimately leading to cell ferroptosis.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 5","pages":"Article 159748"},"PeriodicalIF":3.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052260","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":"Spatial gradients of lipase activity govern lipid droplet remodeling in the zebrafish embryo","authors":"Sudipta Sarkar ,&nbsp;Sayani Haldar ,&nbsp;Subhasis Mandal ,&nbsp;Nandana Nanda ,&nbsp;Subrata Karmakar ,&nbsp;Prosenjit Sen ,&nbsp;Deepak Kumar Sinha","doi":"10.1016/j.bbalip.2026.159747","DOIUrl":"10.1016/j.bbalip.2026.159747","url":null,"abstract":"<div><div>Early zebrafish embryos rely on maternally supplied yolk lipids to fuel growth before the onset of feeding; yet, how these lipids are mobilized and redistributed remains poorly understood. Here, we combine live imaging with the solvatochromic dye Nile Red to map lipid composition in space and time through changes in the emission peak, a readout of local polarity. We show that lipid droplets (LDs) in the blastodisc are highly heterogeneous in size and polarity at the “one-cell stage” but progressively homogenize as development proceeds. LDs originate at the yolk–blastodisc interface, where localized lipase activity drives their biogenesis and initial composition. As LDs migrate toward the animal pole, their polarity increases, reflecting continuous lipolysis within a spatially confined metabolic zone. Smaller LDs display greater lipolytic efficiency than larger ones, linking droplet geometry to metabolic turnover. Inhibition of lipase activity disrupts both LD formation and lipid cycling, demonstrating that shared enzymatic machinery underlies droplet synthesis and degradation. Together, our findings reveal a spatially organized and developmentally regulated lipid metabolism in the zebrafish blastodisc, where local enzyme activity, droplet mechanics, and lipid composition are dynamically coupled. This live-imaging approach establishes a framework for studying lipid regulation in vertebrate development and disease.</div></div><div><h3>Digest summary</h3><div>By visualizing lipids in living zebrafish embryos, this study reveals that lipid droplets are not passive fat stores but dynamic organelles whose size, composition, and behavior are shaped by local enzyme activity at the yolk–blastodisc interface, offering new insight into how developing cells control their energy reserves.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 5","pages":"Article 159747"},"PeriodicalIF":3.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148026392","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":"Maximization of mitochondrial fatty acid oxidation by co-administration of PPARα agonist and peroxisomal β-oxidation inhibitor","authors":"Ziyu Zeng ,&nbsp;Yicong Li ,&nbsp;Junwei Cao ,&nbsp;Wei Zhang,&nbsp;Yida Zhang,&nbsp;Haoya Yao,&nbsp;Yaoqing Wang,&nbsp;Jia Zeng","doi":"10.1016/j.bbalip.2026.159750","DOIUrl":"10.1016/j.bbalip.2026.159750","url":null,"abstract":"<div><div>PPARα plays a pivotal role in regulating hepatic fatty acid oxidation and activation of PPARα has been well known to stimulate mitochondrial β-oxidation and has the potential to reduce hepatic lipid level, while evidences indicate that administration of PPARα agonist does not affect hepatic triglyceride level. Therefore, an alternative mechanism might work to counteract the lipid-lowering effect of PPARα agonist. As fatty acids can also be metabolized in peroxisome and the acetyl-CoA generated in peroxisomal β-oxidation could be used for the biosynthesis of malonyl-CoA, a critical molecule in controlling mitochondria fatty acid oxidation. We hypothesize that peroxisomal β-oxidation might play a role in regulating mitochondrial fatty acid oxidation through mediating malonyl-CoA formation. This study demonstrates a counteracting mechanism by which induction of peroxisomal β-oxidation causes suppression of mitochondrial fatty acid oxidation in animals administered with PPARα agonist. PPARα agonist induces oxidation of fatty acids by peroxisomes and generates considerable acetate in the liver, which significantly elevates hepatic content of malonyl-CoA, and causes suppression of mitochondrial β-oxidation. Specific inhibition of peroxisomal β-oxidation enhances mitochondrial fatty acid oxidation and attenuates hepatic lipid accumulation by reducing acetate and malonyl-CoA formation in the mice treated with PPARα agonist. It is suggested that combination therapy of PPARα agonist and peroxisomal β-oxidation inhibitor might be a novel and effective treatment of fatty liver and related metabolic disorder through maximization of mitochondrial fatty acid oxidation.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 5","pages":"Article 159750"},"PeriodicalIF":3.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052218","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":"Enhydrin from yacon attenuates atherosclerosis by modulating the FABP5/PPARγ/ABCA1 axis: An integrated multi-omics and in vivo validation","authors":"Chao Tian ,&nbsp;Guiping He ,&nbsp;Ling Zu ,&nbsp;Chaoqun Bi ,&nbsp;Zunqiu Wu ,&nbsp;Jianfei Sun","doi":"10.1016/j.bbalip.2026.159751","DOIUrl":"10.1016/j.bbalip.2026.159751","url":null,"abstract":"<div><div>Dysregulated lipid metabolism drives atherosclerosis (AS). Yacon, an Andean lipid-modulating tuber, exerts anti-AS potential, but mechanisms remain unclear. We integrated network pharmacology, machine learning, single-cell RNA sequencing (scRNA-seq), and in vivo validation to explore its anti-AS effects and targets. Active constituents and targets were curated from literature, TCMSP, and SwissTargetPrediction; lipid/AS genes from GeneCards, OMIM, and GEO were filtered via limma, WGCNA, LASSO, randomForest, and SVM-RFE. Immune infiltration and external validation confirmed hub gene relevance. scRNA-seq prioritized FABP5; docking and dynamics quantified compound–FABP5 interactions. In vivo efficacy was tested in high-fat diet (HFD)-fed ApoE−/− mice via histology (Oil Red O, H&amp;E, and Masson) and molecular assays (RT-qPCR, Western blot, and immunofluorescence). We identified 12 constituents, 384 targets, and seven core targets (AURKA, MMP9, FABP5, etc.), with FABP5 top-ranked. Docking and dynamics identified Enhydrin as the strongest FABP5 binder. Enhydrin administration was associated with reduced hepatic lipid accumulation, decreased serum triacylglycerol (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels, and increased high-density lipoprotein cholesterol (HDL<img>C) levels. Histopathological analysis of arterial tissues revealed attenuated vascular lipid deposition and delayed atherosclerotic lesion progression. Across assays, Enhydrin downregulated FABP5, reduced abnormal fatty acid trafficking, and upregulated PPARγ and ABCA1, with markedly reduced vascular lipid deposition and improved serum lipid profiles, reflecting enhanced cholesterol efflux. Conclusion: Our integrative multi-omics analysis pinpointed FABP5 as a promising novel target for yacon-derived Enhydrin in atherosclerosis. In vivo, Enhydrin markedly downregulated FABP5 and upregulated PPARγ and ABCA1, suggesting this axis mediates its anti-atherosclerotic activity.</div></div><div><h3>Significance statement</h3><div>1: This study identified FABP5 as a candidate target for atherosclerosis through integrative multi-omics, and its association with the anti-atherosclerotic effects of Enhydrin suggests therapeutic potential.</div><div>2: The anti-atherosclerotic effects of yacon's active components and their underlying molecular pathways were systematically screened and preliminarily characterized by integrating bioinformatic prediction with in vivo validation, laying a preliminary theoretical foundation for further pharmacological investigation and clinical translation.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 5","pages":"Article 159751"},"PeriodicalIF":3.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148100969","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":"Gm15441 improves adipogenesis and insulin sensitivity by TXNIP regulation in white adipose tissue","authors":"Yinze Shi ,&nbsp;Liying Huang ,&nbsp;Xueyang Yang ,&nbsp;Jiaoyue Zhang ,&nbsp;Lulu Chen","doi":"10.1016/j.bbalip.2026.159718","DOIUrl":"10.1016/j.bbalip.2026.159718","url":null,"abstract":"<div><div><em>Gm15441</em>, a long non-coding RNA antisense to thioredoxin interacting protein (TXNIP) mRNA, exhibits undefined roles in adipogenesis and insulin resistance. This study aimed to explore its functions and mechanisms in white adipose tissue (WAT). <em>Gm15441</em> expression was assessed in 3T3-L1 cells and WAT of insulin-resistant mice. Stable <em>Gm15441</em> overexpression and knockdown 3T3-L1 cell models were established, followed by differentiation induction and analysis of lipid accumulation and differentiation markers. A subcutaneous adipose-specific <em>Gm15441</em> overexpression mouse model was fed high-fat diets (HFD) and evaluated for metabolic parameters, adipogenesis, and insulin signaling. Subcellular localization in vitro was determined via fluorescence in situ hybridization, while transcriptome sequencing, TXNIP expression analysis, and RNA-RNA pull-down assays were performed. Results showed that <em>Gm15441</em> expression increased during cell differentiation and decreased in insulin-resistant WAT. <em>Gm15441</em> overexpression promoted adipogenesis in vitro, while knockdown suppressed it. In HFD-fed mice, adipose-specific <em>Gm15441</em> overexpression enhanced adipogenesis, reduced blood glucose, and improved insulin sensitivity. Although PPARγ expression increased with cell differentiation, <em>Gm15441</em> probes did not pull down PPARγ mRNA. Conversely, TXNIP protein levels decreased in <em>Gm15441</em>-overexpressing cells without corresponding changes in mRNA levels, but <em>Gm15441</em> probes successfully pulled down TXNIP mRNA. These results suggested that <em>Gm15441</em> may promote adipogenesis and enhance insulin sensitivity by inhibiting TXNIP expression.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 3","pages":"Article 159718"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965026","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":"Substituents of the polysaccharide region of LPS in Legionella pneumophila sg1 modulate interactions with host cells","authors":"Bożena Kowalczyk ,&nbsp;Agnieszka Szuster-Ciesielska ,&nbsp;Zbigniew Kaczyński ,&nbsp;Markus Petzold ,&nbsp;Christina E. Galuska ,&nbsp;Beate Fuchs ,&nbsp;Rafal Luchowski ,&nbsp;Wiesław I. Gruszecki ,&nbsp;Piotr Koper ,&nbsp;Adam Choma ,&nbsp;Jacek Tarasiuk ,&nbsp;Marta Palusińska-Szysz","doi":"10.1016/j.bbalip.2026.159720","DOIUrl":"10.1016/j.bbalip.2026.159720","url":null,"abstract":"<div><div><em>Legionella pneumophila</em> is a Gram-negative bacterium commonly found in natural freshwater reservoirs, where it exists as an intracellular parasite of cohabiting protozoa, primarily of the genus <em>Acanthamoeba</em>. Inhalation of aerosol contaminated with the bacterium leads to its proliferation within pulmonary macrophages, ultimately resulting in pneumonia known as Legionnaires' disease. The lipopolysaccharide (LPS) of <em>L. pneumophila</em> sg1 constitutes the most exposed component of the bacterial cell wall, playing a key role in every stage of its developmental cycle associated with host cells. The <em>orf8</em> gene encodes an <em>N</em>-methyltransferase responsible for the methylation of the 5-acetimidoylamino group in legionaminic acid of LPS of <em>L. pneumophila</em> sg1 strain 130b. Mutants impaired in synthesizing <em>N</em>-methyl groups of legionaminic acid produce neutral lipids, sphingolipids, and ceramides with an altered composition compared to the wild-type strain. <em>N</em>-methyl groups in legionaminic acid enhance bacterial adhesion to <em>Acanthamoeba castellanii</em> cells and THP-1-derived macrophages. Their occurrence, however, reduces the adhesion capacity of <em>L. pneumophila</em> sg1 strain 130b to epithelial cells of the A549 and BEAS-2B lines.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 3","pages":"Article 159720"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986713","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":"Palmitoylated STX11 suppresses AMPK to drive lipogenesis and colorectal cancer","authors":"Bao Li ,&nbsp;Zhongkang Yan ,&nbsp;Wenyuan Dang ,&nbsp;Jianxiong Han ,&nbsp;Hongli Xue ,&nbsp;Feifei Wang ,&nbsp;Lili Wang ,&nbsp;Xueqing Yang ,&nbsp;Xingyuan Yang","doi":"10.1016/j.bbalip.2026.159730","DOIUrl":"10.1016/j.bbalip.2026.159730","url":null,"abstract":"<div><div>Syntaxin 11(STX11), a SNARE family protein, regulates vesicular trafficking and cytokinesis, yet its functional role in colorectal cancer (CRC) pathogenesis remains poorly understood. Here, we identify STX11 as a critical regulator that potentiates CRC progression in vivo and in vitro. Mechanistically, STX11 modulates the AMPK signaling pathway in a palmitoylation-dependent manner, attenuating ACC phosphorylation to enhance its enzymatic activity and stimulate de novo lipogenesis. Genetic ablation of STX11 significantly impedes tumorigenesis in an AOM/DSS-induced CRC mouse model. Our findings establish STX11 as a critical regulator of lipid metabolism in CRC progression and nominate it as a promising therapeutic target.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 3","pages":"Article 159730"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099818","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}