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

{"title":"The role of ancient ubiquitous protein 1 (Aup1) in regulating hepatic lipid droplet levels, endoplasmic reticulum stress, and inflammation in zebrafish (Danio rerio).","authors":"Shuangyang Xu, Yanan Shen, Zengqi Zhao, Kangsen Mai, Qinghui Ai","doi":"10.1016/j.bbalip.2025.159643","DOIUrl":"https://doi.org/10.1016/j.bbalip.2025.159643","url":null,"abstract":"<p><p>Excessive supplementation of palm oil (PO) in aquafeeds induces hepatic endoplasmic reticulum (ER) stress and inflammatory responses in fish, while lipid droplet (LD) formation has been demonstrated to alleviate stress and inflammation by sequestering lipotoxic lipids. Studies in mammals indicate that ancient ubiquitous protein 1 (Aup1) is a LD-associated protein participating in ER-associated degradation (ERAD) and LD regulation. However, whether Aup1 is involved in the regulation of hepatic LD metabolism, ER stress, and inflammatory responses has not been elucidated in fish. In this study, we cloned zebrafish (Danio rerio) aup1, conducted sequence analysis, and established in vitro hepatocyte models with Aup1 overexpression and knockdown through electroporation of plasmids. Bioinformatics analysis identified zebrafish Aup1 as an unstable, alkaline, hydrophilic transmembrane protein. Subcellular localization demonstrated dual localization of Aup1 on LDs and the ER. Tissue distribution experiments revealed Aup1 was ubiquitously expressed in multiple tissues, with the highest expression in the liver. RT-qPCR and Western blot showed that PO significantly upregulated Aup1 expression in vivo and in vitro, and dual-luciferase reporter assays identified Atf4a as an important transcriptional activator of zebrafish aup1 promoter. Aup1 overexpression markedly improved LD levels as well as triglyceride (TG) content, and reduced ER stress-related genes and pro-inflammatory cytokines expression in zebrafish liver (ZFL) cells. Conversely, Aup1 knockdown exerted opposite effects. These findings indicated that Aup1 could promote LD biogenesis and mitigate ER stress and inflammation. This study may provide novel insights for developing therapeutic strategies against PO-induced hepatic damage in cultured fish species.</p>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":" ","pages":"159643"},"PeriodicalIF":3.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246231","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":"Tumor necrosis factor alpha-induced activation of SREBP2 promotes cholesterol biosynthesis in cholestasis","authors":"Ziqian Xu ,&nbsp;Xinyu Cao ,&nbsp;Zhixian Zhu,&nbsp;Jiaxin Lei,&nbsp;Ling Li,&nbsp;Xiaoxun Zhang,&nbsp;Jin Chai","doi":"10.1016/j.bbalip.2025.159642","DOIUrl":"10.1016/j.bbalip.2025.159642","url":null,"abstract":"<div><h3>Background and aims</h3><div>Cholestasis is frequently associated with lipid metabolism disorders, elevated cholesterol levels and disruptions in bile acid homeostasis. Nevertheless, the mechanisms underlying cholesterol elevation in cholestasis remain inadequately understood. This study aims to investigate alterations in cholesterol levels and potential mechanisms in mouse models of cholestasis. Additionally, we evaluate the therapeutic potential of Sterol Regulatory Element Binding Protein 2 (SREBP2), a key transcription factor regulating cholesterol synthesis, in treating cholestasis.</div></div><div><h3>Approaches and results</h3><div>We developed mouse models of cholestasis using bile duct ligation (BDL) and a 0.1 % 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Serum and liver samples were collected for analysis. The human hepatoma cell line PLC/RPF/5 was used for mechanistic studies. Cholestatic mice exhibited significantly elevated total cholesterol levels in serum and liver. Gene expression analysis revealed marked upregulation of cholesterol biosynthesis-related genes and the transcription factor SREBP2. Mechanistic studies indicated that TNFα promotes cholesterol synthesis by activating SREBP2 and its downstream target genes. To validate these findings in vivo, we employed the BDL mouse model and treated the mice with Fatostatin, a known SREBP2 inhibitor. Administration of Fatostatin significantly reduced serum ALT, ALP and hepatic cholesterol levels in the BDL mouse model, suggesting a potential therapeutic effect against cholestatic liver injury.</div></div><div><h3>Conclusions</h3><div>This study concludes that the activation of the NF-κB signaling pathway by TNFα leads to increased expression of SREBP2 in cholestatic mouse model. These findings indicate that the TNFα/NF-κB/SREBP2 pathway could serve as a promising target for treating cholestasis.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159642"},"PeriodicalIF":3.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144239789","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":"Advances in lipid research: From bench to bedside","authors":"Gwendolyn Barceló-Coblijn ,&nbsp;Jesús Balsinde","doi":"10.1016/j.bbalip.2025.159624","DOIUrl":"10.1016/j.bbalip.2025.159624","url":null,"abstract":"","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159624"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972917","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":"Phosphoinositide acyl chain diversity: comparative analysis across species and mouse tissues","authors":"David Barneda ,&nbsp;Vishnu Janardan ,&nbsp;John Swales ,&nbsp;Maria Ciaccia ,&nbsp;Richard Goodwin ,&nbsp;Sabina Cosulich ,&nbsp;Padinjat Raghu ,&nbsp;Jonathan Clark ,&nbsp;Len Stephens ,&nbsp;Phillip Hawkins","doi":"10.1016/j.bbalip.2025.159640","DOIUrl":"10.1016/j.bbalip.2025.159640","url":null,"abstract":"<div><div>Cells create acyl chain compositions for their phosphoinositide (PIPn) pools that are distinct from other phospholipid classes. While some lower eukaryotes present highly heterogeneous PIPn (e.g., yeast, fly), more complex organisms typically display PIPn enriched in fewer molecular species (e.g., the C38:4 species in fish, frog and mice). A comprehensive analysis of murine tissues (using both LC-MS/MS and MSI) confirms a general enrichment for C38:4-PIPn but also highlights the existence of several cell populations with strikingly divergent acyl chain compositions, characterised by the prevalence of shorter-chain, more saturated species (e.g., C32:0 in the testes and C34:1 in the prostate). The evolutionary pressures driving the creation of these specific acyl chain compositions are still unclear; current evidence suggests there is probably a balance to be achieved in different cell types between the biophysical constraints imposed by PIPn as membrane-captive ‘messengers’ (e.g., flexibility in head group presentation in different membrane environments), the demand for substantial de novo lipid synthesis (e.g., in rapid membrane expansion), the need for acyl chain remodelling (e.g., in molecular segregation of functional pools) and fatty acid availability. Moreover, it would appear inevitable that this balance will be distorted under most cell culture conditions in vitro<em>.</em></div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159640"},"PeriodicalIF":3.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186432","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":"Neurogenin 2-induced central neurons from iPSC-established patients with NPC display attenuated neurite outgrowth while accumulating cholesterol.","authors":"Miki Igarashi, Takashi Miyajima, Chen Wu, Takeo Iwamoto, Yoshikatsu Eto","doi":"10.1016/j.bbalip.2025.159639","DOIUrl":"https://doi.org/10.1016/j.bbalip.2025.159639","url":null,"abstract":"<p><p>Niemann-Pick disease type C (NPC) is a lysosome disease hallmarked by autosomal recessive mutations in the NPC1 or NPC2 genes. It results in the accumulation of unesterified cholesterol in the late endosome/lysosome compartment, and then induces progressive neurodegeneration in affected individuals. Previous studies have primarily used fibroblasts derived from NPC patients to examine the cellular pathology and test therapeutic agents. However, the neurodegenerative aspect of the disease should be clarified using an in vitro system that recapitulates the cellular mechanisms underlying the neuronal defects. In this study, we generated iPSCs from NPC patients, and differentiated them into neurons to examine the pathological and biological defects in NPC neurons. Five iPSCs (3 NPC and 2 healthy individuals) carrying a doxycycline-inducible NGN2 (iPSCs^TetON:NGN2) were generated, and edited cells efficiently differentiated into cortical neurons by 15 days. Although the standard differentiated culture method did not show any phenotypic features in NPC neurons, human-derived low-density lipoprotein (LDL) treatment exhibited cellular pathological features, including the accumulation of unesterified cholesterol and impaired neurite outgrowth. Miglustat, a drug approved for NPC in several countries, promoted neurite outgrowth and reduced unesterified cholesterol accumulation in LDL-treated NPC neurons. Using our model, two drugs among an FDA-approved drug library attenuated the pathological defects by LDL treatment. Collectively, our results indicate that neurons of NPC patients fail neurite extension due to suboptimal cholesterol transport to the membrane. This will be a valuable tool for NPC research to identify the pathological mechanisms of neuronal degeneration and to discover new therapeutics.</p>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":" ","pages":"159639"},"PeriodicalIF":3.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172621","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":"Laminar shear stress promotes accumulation of polyunsaturated fatty acid in aortic endothelial cells through upregulation of LPCAT3 enzyme activity","authors":"Delphine Bousquet ,&nbsp;Nicolas Guillot","doi":"10.1016/j.bbalip.2025.159638","DOIUrl":"10.1016/j.bbalip.2025.159638","url":null,"abstract":"<div><h3>Objective</h3><div>Endothelial cells (ECs) play an important role in tissue homeostasis. Hemodynamic laminar shear stress are involved in both the physiological and pathological function of endothelial cells EC. Lipid metabolism has emerged as a potential regulator of EC function. Here, we aim to decipher the role of laminar shear stress in the regulation of lipid metabolism in human aortic endothelial cells.</div></div><div><h3>Approach and results</h3><div>Human aortic endothelial cells (HAOEC) were exposed to laminar shear stress, and lipid metabolism was analyzed. We found that laminar flow increased polyunsaturated fatty acid (PUFA) content in both neutral and polar lipids. These changes in fatty acid composition were dependent on lysophosphatidylcholine acyltransferase 3 (LPCAT3), which was specifically upregulated by laminar shear stress at both the mRNA and activity levels. Fatty acid uptake was also modulated by shear stress, partly <em>via</em> the LXR pathway. Notably, mechanical stimulation did not alter <em>de novo</em> fatty acid synthesis. However, fatty acid oxidation was upregulated in response to laminar shear stress, involving AMPK and ACC phosphorylation. These modifications in HAOEC fatty acid composition ultimately led to the release of a distinct pattern of lipid metabolites.</div></div><div><h3>Conclusion</h3><div>Overall these data revealed that laminar shear stress increased the turnover of FA acid and in human aortic endothelial cells through the activation of the LPCAT 3 enzyme.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159638"},"PeriodicalIF":3.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130799","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":"Reduced cholesterol alters the biophysical properties of repaired myelin","authors":"Estephanie L. Nottar Escobar ,&nbsp;Nishama De Silva Mohotti ,&nbsp;Mara Manolescu ,&nbsp;Anika Radadiya ,&nbsp;Prajnaparamita Dhar ,&nbsp;Meredith D. Hartley","doi":"10.1016/j.bbalip.2025.159637","DOIUrl":"10.1016/j.bbalip.2025.159637","url":null,"abstract":"<div><div>The myelin sheath is a lipid-rich membrane that ensheathes axons and is required for healthy and efficient signal transduction. Myelin is damaged in neurological diseases like multiple sclerosis, but remyelination can occur through the action of oligodendrocyte precursor cells (OPCs), which differentiate into mature oligodendrocytes that wrap axons to form repaired myelin. In this study, a genetic-based mouse model of demyelination was used, which features near-complete demyelination followed by robust remyelination in the brain. Lipid mass spectrometry on isolated myelin from the remyelinated brain revealed a decrease in the percent mole fraction of cholesterol when compared to healthy myelin. Biophysical studies on monomolecular lipid films formed using repaired myelin lipid extracts showed changes in the surface behavior of the lipid films, compared to the healthy myelin lipids. Films formed using the remyelinated lipid extracts resulted in lower surface pressures and lower compressional moduli when compared to healthy controls, suggesting that repaired myelin membranes have lower lateral molecular packing within the lipid film. Synthetically prepared model membranes, based on the major lipid compositions of the healthy and diseased extracts, revealed that changes in cholesterol levels were the primary contributor to the changes in biophysical properties. Supplementation of the diseased lipid extracts with cholesterol led to a robust improvement in membrane surface pressures and compressibility. Together, these results suggest that high cholesterol levels are required for myelin membrane stability and that reduced cholesterol in repaired myelin may have a profound impact on the biophysical properties of the myelin membrane.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159637"},"PeriodicalIF":3.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123574","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":"Rapamycin induced autophagy enhances lipid breakdown and ameliorates lipotoxicity in Atlantic salmon cells","authors":"Kanchan Phadwal ,&nbsp;Jennifer Haggarty ,&nbsp;Dominic Kurian ,&nbsp;Judit Aguilar Martí ,&nbsp;Jianxuan Sun ,&nbsp;Ross D. Houston ,&nbsp;Mónica B. Betancor ,&nbsp;Vicky E. MacRae ,&nbsp;Phillip D. Whitfield ,&nbsp;Daniel J. Macqueen","doi":"10.1016/j.bbalip.2025.159636","DOIUrl":"10.1016/j.bbalip.2025.159636","url":null,"abstract":"<div><div>Autophagy is a highly conserved cellular recycling process essential for homeostasis in all eukaryotic cells. Lipid accumulation and its regulation by autophagy are key areas of research for understanding metabolic disorders in human and model mammals. However, the role of autophagy in lipid regulation remains poorly characterized in non-model fish species of importance to food production, which could be important for managing health and welfare in aquaculture. Addressing this knowledge gap, we investigate the role of autophagy in lipid regulation using a macrophage-like cell line (SHK-1) from Atlantic salmon (<em>Salmo salar</em> L.), the world's most commercially valuable farmed finfish. Multiple lines of experimental evidence reveal that the autophagic pathway responsible for lipid droplet breakdown is conserved in Atlantic salmon cells. We employed global lipidomics and proteomics analyses on SHK-1 cells subjected to lipid overload, followed by treatment with rapamycin to induce autophagy. This revealed that activating autophagy via rapamycin enhances storage of unsaturated triacylglycerols and suppresses key lipogenic proteins, including fatty acid elongase 6, fatty acid binding protein 2 and acid sphingomyelinase. Moreover, fatty acid elongase 6 and fatty acid binding protein 2 were identified as possible cargo for autophagosomes, suggesting a critical role for autophagy in lipid metabolism in fish. Together, this study establishes a novel model of lipotoxicity and advances understanding of lipid autophagy in fish cells, with significant implications for addressing fish health issues in aquaculture.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159636"},"PeriodicalIF":3.9,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101227","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":"DHA suppresses hormone-sensitive and castration-resistant prostate cancer growth by decreasing de novo lipogenesis","authors":"G.H. Tamarindo ,&nbsp;C.F. Ribeiro ,&nbsp;S. Rodrigues ,&nbsp;R.M. Góes ,&nbsp;M. Loda","doi":"10.1016/j.bbalip.2025.159634","DOIUrl":"10.1016/j.bbalip.2025.159634","url":null,"abstract":"<div><h3>Objective</h3><div><em>De novo</em> lipogenesis (DNL) is associated with prostate cancer (PCa) progression, while fatty acid synthase (FASN) overexpression is a hallmark of DNL. Palmitate, its main product, is a saturated fatty acid that supports PCa growth. Polyunsaturated fatty acids (PUFAs), which can be acquired from the microenvironment, undergo peroxidation more readily and affect membrane fluidity. Docosahexaenoic acid (DHA) is a prototype PUFA omega-3 produced inefficiently in human cells. Its levels are low in PCa cells compared to normal cells. We hypothesize that excess DHA may reprogram lipid metabolism and induce cell growth suppression.</div></div><div><h3>Methods</h3><div>Androgen-responsive LNCaP, castration-resistant cells C4–2 and 22Rv1, human PCa castration-resistant organoids, and prostate cancer xenografts were exposed to DHA.</div></div><div><h3>Results</h3><div>DHA accumulated into lipid droplets as triacylglycerols and cholesterol esters, led to increased phospholipid acyl chain unsaturation and altered phospholipid ratio, a known trigger of endoplasmic reticulum (ER) stress. DHA caused a decrease in sterol regulatory element-binding protein (SREBP) transcriptional program, which, in turn, led to decreased expression of FASN. The subsequent reduction in DNL caused downregulation of the androgen receptor (AR) and its splice variant AR-V7. In addition, β-oxidation was enhanced, and DHA was preferentially oxidized over palmitate. Glucose oxidation also increased in the presence of DHA. Finally, DHA led to ROS overproduction, oxidative damage, and ER stress.</div></div><div><h3>Conclusions</h3><div>DHA reduces the growth of hormone-sensitive and castration-resistant PCa both <em>in vitro</em> and <em>in vivo via</em> deregulation of lipid metabolism.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159634"},"PeriodicalIF":3.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092480","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":"Lauric acid ameliorates excessive linoleic acid induced macrophage inflammatory response and oxidative stress in large yellow croaker (Larimichthys crocea)","authors":"Yuhang Tang ,&nbsp;Yanan Shen ,&nbsp;Wencong Lai ,&nbsp;Chuanwei Yao ,&nbsp;Changxu Sui ,&nbsp;Tingting Hao ,&nbsp;Jianlong Du ,&nbsp;Yueru Li ,&nbsp;Kangsen Mai ,&nbsp;Qinghui Ai","doi":"10.1016/j.bbalip.2025.159635","DOIUrl":"10.1016/j.bbalip.2025.159635","url":null,"abstract":"<div><div>Macrophages are particularly prone to inflammation and oxidative stress upon exogenous stimulus. Previous investigations have shown that lauric acid (LRA) exerts anti-inflammatory and antioxidant effects, however, the molecular mechanism remains elusive. This study aims to elucidate the function and molecular mechanisms by which LRA provided a defense against inflammation and oxidative stress brought by linoleic acid (LA), both <em>in vivo</em> and <em>in vitro</em>. Feeding trial results indicated that dietary LA led to severe inflammation and impaired antioxidant capacity in head kidney of large yellow croaker. The gene and protein expressions of inflammation-related were upregulated and those of antioxidant defense were down-regulated in the LA diet group, which were reversed by glycerol monolaurate (LRA derivative). Meanwhile, in macrophages, LRA suppressed the expressions of p-ERK and p-JNK and the gene expressions of pro-inflammatory factors induced by excessive LA. G protein coupled receptor 84 (GPR84, endogenous receptor of LRA) disturbance did not alter LRA-induced ERK and JNK MAPK pathways and pro-inflammatory gene expressions decline. Besides, LRA decreased reactive oxygen species (ROS) level and increased the expressions of nuclear factor erythroid 2-related factor 2 (NRF2). And blockage of NRF2 reversed the protective effect of LRA-mediated the protection against oxidative stress. Collectively, these results demonstrated that LRA attenuated LA-induced inflammation by suppressing ERK and JNK MAPK pathways and oxidative stress by activating NRF2 signaling in macrophages. These findings revealed that the function and molecular mechanisms of LRA alleviating inflammation and oxidative stress in macrophages, which provides new insights for enhancing immune cell function in vertebrates.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 6","pages":"Article 159635"},"PeriodicalIF":3.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092542","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}