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

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Cytoskeleton regulates lipid droplet fusion and lipid storage by controlling lipid droplet movement 细胞骨架通过控制脂滴的运动来调节脂滴的融合和储存。
IF 3.9 2区 生物学
Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-04-04 DOI: 10.1016/j.bbalip.2025.159610
Yan Liang , Zanzan Zhu , Yiming Lu , Chengxin Ma , Jiacheng Li , Kuan Yu , Jin Wu , Xinmeng Che , Xu Liu , Xiaoxiao Huang , Peng Li , Feng-Jung Chen
{"title":"Cytoskeleton regulates lipid droplet fusion and lipid storage by controlling lipid droplet movement","authors":"Yan Liang ,&nbsp;Zanzan Zhu ,&nbsp;Yiming Lu ,&nbsp;Chengxin Ma ,&nbsp;Jiacheng Li ,&nbsp;Kuan Yu ,&nbsp;Jin Wu ,&nbsp;Xinmeng Che ,&nbsp;Xu Liu ,&nbsp;Xiaoxiao Huang ,&nbsp;Peng Li ,&nbsp;Feng-Jung Chen","doi":"10.1016/j.bbalip.2025.159610","DOIUrl":"10.1016/j.bbalip.2025.159610","url":null,"abstract":"<div><div>Lipid droplets (LDs) are highly dynamic organelles that maintain cellular lipid homeostasis through size and number control. In adipose tissue, CIDEC plays a crucial role in LD fusion and lipid homeostasis. However, the regulatory factors and mechanisms of LD fusion remain largely unknown. Here, we established a high-throughput LD phenotypic screen on a compound library consisting of 2010 small molecules, and identified 11 cytoskeleton inhibitors that negatively regulate LD size. Using specific inhibitors against each of the three types of cytoskeleton, our data showed that the disruption of microtubules and microfilaments but not intermediate filaments limits CIDEC-mediated LD fusion and growth by reducing LD movement and LD-LD contact. The collective effect of microtubule inhibitors results in a small LD phenotype which favors lipolysis upon activation of cAMP-PKA pathway in adipocytes. Our findings demonstrate that cytoskeleton is involved in the process of LD fusion and growth, indicating their role in lipid storage metabolism.</div><div><strong>One-Sentence Summary:</strong> Cytoskeleton regulates lipid droplet fusion and lipid storage</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 4","pages":"Article 159610"},"PeriodicalIF":3.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794644","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}
引用次数: 0
Lipid metabolism associated PLPP4 gene drives oncogenic and adipogenic potential in breast cancer cells 脂质代谢相关的PLPP4基因驱动乳腺癌细胞的致癌和成脂潜能。
IF 3.9 2区 生物学
Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-04-03 DOI: 10.1016/j.bbalip.2025.159609
Sneha Soni, Sweta H. Makwana, Shivani Bansal, Monika Kumari, Chandi C. Mandal
{"title":"Lipid metabolism associated PLPP4 gene drives oncogenic and adipogenic potential in breast cancer cells","authors":"Sneha Soni,&nbsp;Sweta H. Makwana,&nbsp;Shivani Bansal,&nbsp;Monika Kumari,&nbsp;Chandi C. Mandal","doi":"10.1016/j.bbalip.2025.159609","DOIUrl":"10.1016/j.bbalip.2025.159609","url":null,"abstract":"<div><div>Lipid metabolic reprogramming plays a pivotal role in cancer cell evolution and causing subsequent cancer growth, metastasis and therapy resistance. Cancer associated adipocyte and/or cancer derived adipocyte-like cells often supply fuels and various factors to fulfill the cells bioenergetics to enhance oncogenic potential. This study intends to find out a set of dysregulated genes involved in lipid metabolism in breast cancer studies and uncovers the role of unexplored dysregulated gene in cancer potential. Cancer database analysis determines seven seed signature genes (PLPP2, PLPP4, CDS1, ASAH2, LCLAT1, LPCAT1 and LASS6/CERS6) concluded from relative expression and survival analysis. Furthermore, experimental analysis unveils the gene PLPP4 (Phospholipid Phosphatase 4) as oncogene confirmed by knockdown and overexpression studies in MDA-MB 231 and MCF-7 breast cancer cells. PLPP4 enzyme is involved in regulation of triacyl glycerol metabolism. Lipid accumulation along with other studies documented enhanced lipid droplets, TAG formation and glycerol release with concomitant increased expressions of various adipogenic markers (<em>e.g.</em>, PPARγ, perilipin 1 and leptin) in breast cancer cells transfected with PLPP4 gene expressing plasmid whereas downregulation of PLPP4 gene diminished lipid accumulation and adipocyte marker gene expressions. Our findings also revealed that BMP2 induced adipogenic potential in breast cancer cells was mitigated in response to downregulation of PLPP4 gene expression. All these findings together, for first time, demonstrated that BMP2 drives PLPP4 to enhance both oncogenic and adipogenic potential in breast cancer cells. This article uncovers the perturbed lipid metabolism associated PLPP4 acts as oncogene presumably by modulating adipogenic activity in cancer cells.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159609"},"PeriodicalIF":3.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787652","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}
引用次数: 0
Alterations in phosphatidylethanolamine metabolism impacts hepatocellular lipid storage, energy homeostasis, and proliferation 磷脂酰乙醇胺代谢的改变影响肝细胞脂质储存、能量稳态和增殖
IF 3.9 2区 生物学
Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-03-26 DOI: 10.1016/j.bbalip.2025.159608
Courtney M. Holdaway , Kelly-Ann Leonard , Randal Nelson , Jelske van der Veen , Chinmayee Das , Russell Watts , Robin D. Clugston , Richard Lehner , Rene L. Jacobs
{"title":"Alterations in phosphatidylethanolamine metabolism impacts hepatocellular lipid storage, energy homeostasis, and proliferation","authors":"Courtney M. Holdaway ,&nbsp;Kelly-Ann Leonard ,&nbsp;Randal Nelson ,&nbsp;Jelske van der Veen ,&nbsp;Chinmayee Das ,&nbsp;Russell Watts ,&nbsp;Robin D. Clugston ,&nbsp;Richard Lehner ,&nbsp;Rene L. Jacobs","doi":"10.1016/j.bbalip.2025.159608","DOIUrl":"10.1016/j.bbalip.2025.159608","url":null,"abstract":"<div><div>Phosphatidylethanolamine (PE) is the second most abundant glycerophospholipid in eukaryotic membranes and is involved in several cellular processes. An important pathway for <em>de novo</em> PE synthesis is the Kennedy Pathway. The rate limiting enzyme in the pathway, CTP:phosphoethanolamine cytidyltransferase, catalyzes the synthesis of CDP-ethanolamine from phosphoethanolamine (pEtn) and CTP. Ethanolamine phosphate phospholyase (ETNPPL) has the potential to breakdown pEtn by catabolizing it to form acetaldehyde, ammonium, and inorganic phosphate. Research on this enzyme is limited and it is unclear how its activity affects PE synthesis; therefore, an investigation into ETNPPL's biological effects is required.</div><div>ETNPPL was expressed in human hepatoma cell line (Huh7) by stable transfection, allowing for long-term expression in cells without ETNPPL. We show that ETNPPL reduces cellular pEtn synthesized from ethanolamine, which decreased synthesis of PE and an increased PC:PE ratio, which has been shown to be associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and impaired mitochondrial function. Experiments conducted show increased neutral lipid storage accompanied by decreased ATP production and oxygen consumption; however, no differences in triglyceride secretion were seen, although ApoB100 secretion was reduced. Huh7 cells expressing ETNPPL proliferate at a slower rate than control and have increased mRNA expression of <em>p53</em> and tumor suppressor genes (<em>CDKN1A, BBC3, BAX, BRCA1)</em>, implicating ETNPPL in cell proliferation, cancer development and/or tumor progression. Overall, ETNPPL rewires hepatic lipid metabolism, altering several processes including increasing lipid storage and decreasing proliferation. The impacts observed in this study may create a link between hepatic ETNPPL expression and MASLD/HCC pathophysiology.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 4","pages":"Article 159608"},"PeriodicalIF":3.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735154","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
Walnut oil as a dietary intervention for atherosclerosis: Efficacy and mechanistic pathways 核桃油作为饮食干预动脉粥样硬化:功效和机制途径
IF 3.9 2区 生物学
Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-03-08 DOI: 10.1016/j.bbalip.2025.159607
Shujuan Hu , Si Tang , Dang Liu , Ruohan Xia , Xianwang Wang
{"title":"Walnut oil as a dietary intervention for atherosclerosis: Efficacy and mechanistic pathways","authors":"Shujuan Hu ,&nbsp;Si Tang ,&nbsp;Dang Liu ,&nbsp;Ruohan Xia ,&nbsp;Xianwang Wang","doi":"10.1016/j.bbalip.2025.159607","DOIUrl":"10.1016/j.bbalip.2025.159607","url":null,"abstract":"<div><h3>Background and aims</h3><div>Walnut oil (WO) and peanut oil (PO) are common vegetable oils rich in unsaturated fatty acids, known to alleviate atherosclerosis (AS) and reduce the risk of cardiovascular diseases (CVD). WO contains a higher proportion of polyunsaturated fatty acids (PUFAs) compared to PO. This study aimed to explore the influence of WO on AS and elucidate its potential mechanisms, providing a theoretical basis for enhancing the application of WO in functional foods and pharmaceuticals.</div></div><div><h3>Methods</h3><div>AS was established in rats using a high-fat diet and vitamin D3 injections. Rats with AS were administered WO or PO via gavage at a dose of 1.2 g/kg for 4 weeks. Serum lipid levels and arterial injury were assessed, and transcriptomic and metabolomic analyses of the rat vasculature were performed.</div></div><div><h3>Results</h3><div>Both WO and PO significantly lowered serum lipid levels and the atherogenic index (AI) in rats, reducing arterial wall injury and plaque formation. WO exhibited a more pronounced effect, particularly in decreasing serum levels of TG, TC, HDL<img>C, and LDL-C. Transcriptomic analysis indicated that fatty acid, amino acid metabolism were crucial in AS development due to a high-fat diet. Metabolomic analysis indicated significant changes in the metabolism of arginine, proline, cysteine, methionine, glycine, serine and threonine in rats treated with WO.</div></div><div><h3>Conclusion</h3><div>WO and PO help alleviate AS by regulating lipid metabolism and influencing pivotal metabolic pathways like TCA cycle and cysteine-methionine metabolism. The more significant impact of WO indicates its potential as a dietary supplement for preventing and treating AS.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 4","pages":"Article 159607"},"PeriodicalIF":3.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143593432","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}
引用次数: 0
Curcumin inhibits pancreatic steatosis in mice with a high-fat diet through the YAP/p53 pathway and confirmed through ultrasonic imaging 姜黄素通过YAP/P53通路抑制高脂饮食小鼠胰腺脂肪变性,并经超声显像证实。
IF 3.9 2区 生物学
Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-02-21 DOI: 10.1016/j.bbalip.2025.159605
Helin Ke , Ziwei Xu , Lina Han , Han Wang , Guorong Lyu , Shilin Li
{"title":"Curcumin inhibits pancreatic steatosis in mice with a high-fat diet through the YAP/p53 pathway and confirmed through ultrasonic imaging","authors":"Helin Ke ,&nbsp;Ziwei Xu ,&nbsp;Lina Han ,&nbsp;Han Wang ,&nbsp;Guorong Lyu ,&nbsp;Shilin Li","doi":"10.1016/j.bbalip.2025.159605","DOIUrl":"10.1016/j.bbalip.2025.159605","url":null,"abstract":"<div><h3>Aims</h3><div>To investigate the mechanism by which curcumin inhibits pancreatic steatosis (PS), and the diagnostic value of ultrasonography in the pancreas of mice with obesity.</div></div><div><h3>Materials and methods</h3><div>Male mice were randomly divided into normal chow diet (NC), high-fat diet (HFD), and HFD + 80 mg/kg curcumin groups (HC) and maintained for 12 weeks to induce PS. Weight and fasting blood glucose (FBG) were collected biweekly and oral glucose tolerance test and insulin levels were measured in the final week. The morphology and fat infiltration of pancreas were observed by ultrasonography and histology. The level of blood lipid was detected, and the expression of genes and proteins related to lipid metabolism in pancreatic tissues was analyzed.</div></div><div><h3>Results</h3><div>Compared to the NC and HC groups, the HFD group had higher body weight, cholesterol, triglycerides, and LDL and HDL levels, along with increased inflammation and fat deposits in the pancreas. The HC group had milder inflammation and lower glucose intolerance and insulin resistance (<em>P</em>&lt;0.05). The gray value, steatosis scores, immunohistochemical results, and ORO staining were significantly correlated (<em>P</em>&lt;0.05). Correlations were found between gray values, steatosis scores, and ORO staining (<em>P</em>&lt;0.05). In comparison to the HFD, expression of LATS2, FAS, YAP, and SREBP2 were downregulated and p53 was upregulated in the HC group.</div></div><div><h3>Conclusion</h3><div>Curcumin is a potential modulator of insulin resistance and SREBP2 expression, with its underlying mechanism possibly mediated through the YAP/p53 signaling pathway. Pancreatic steatosis exhibits distinct ultrasonographic features, making ultrasound an effective diagnostic tool for identifying the condition.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 3","pages":"Article 159605"},"PeriodicalIF":3.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482133","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}
引用次数: 0
Preventive effect of siphonaxanthin, a carotenoid from green algae, against diabetic nephropathy and lipid metabolism insufficiency in skeletal muscle 绿藻类胡萝卜素虹黄质对糖尿病肾病和骨骼肌脂质代谢不足的预防作用
IF 3.9 2区 生物学
Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-02-20 DOI: 10.1016/j.bbalip.2025.159604
Jiawen Zheng, Yuki Manabe, Tatsuya Sugawara
{"title":"Preventive effect of siphonaxanthin, a carotenoid from green algae, against diabetic nephropathy and lipid metabolism insufficiency in skeletal muscle","authors":"Jiawen Zheng,&nbsp;Yuki Manabe,&nbsp;Tatsuya Sugawara","doi":"10.1016/j.bbalip.2025.159604","DOIUrl":"10.1016/j.bbalip.2025.159604","url":null,"abstract":"<div><div>Diabetic nephropathy is a complication of diabetes mellitus characterized by the gradual progression of renal insufficiency, resulting in renal failure. Approximately 15 % or more of patients with type 2 diabetes mellitus have diabetic nephropathy. Siphonaxanthin is a green algal carotenoid noted for its strong biological activities, including anti-obesity effects. In this study, we aimed to evaluate the preventive effects of siphonaxanthin on diabetic nephropathy using db/db mice as a type 2 diabetes mellitus and diabetic nephropathy model. Ingestion of AIN-93G containing 0.004 % w/w siphonaxanthin did not improve plasma creatinine and urine albumin levels but significantly mitigated renal morphological changes in diabetic mice. Moreover, siphonaxanthin restored the decreased mRNA expression of fatty acid β-oxidation-related proteins in the skeletal muscle. These results indicate that siphonaxanthin can potentially ameliorate type 2 diabetes mellitus-induced kidney damage and lipid metabolism insufficiency in skeletal muscle. This study provides a possible daily nutraceutical solution for treating diabetic nephropathy and lipid metabolic abnormalities.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 3","pages":"Article 159604"},"PeriodicalIF":3.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464188","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}
引用次数: 0
Production, characterization and biodistribution of therapeutic high-density lipoprotein-like nanoparticles reconstituted with or without histidine-tagged recombinant ApoA1 含或不含组氨酸标记的重组ApoA1重组的治疗性高密度脂蛋白样纳米颗粒的生产、表征和生物分布
IF 3.9 2区 生物学
Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-02-20 DOI: 10.1016/j.bbalip.2025.159606
Sarah Rosanaly , Marie Laurine Apalama , Matthieu Bringart , Pierre Giraud , Benoit Allard , Bryan Veeren , Olivier Meilhac , Joël Couprie , Philippe Rondeau
{"title":"Production, characterization and biodistribution of therapeutic high-density lipoprotein-like nanoparticles reconstituted with or without histidine-tagged recombinant ApoA1","authors":"Sarah Rosanaly ,&nbsp;Marie Laurine Apalama ,&nbsp;Matthieu Bringart ,&nbsp;Pierre Giraud ,&nbsp;Benoit Allard ,&nbsp;Bryan Veeren ,&nbsp;Olivier Meilhac ,&nbsp;Joël Couprie ,&nbsp;Philippe Rondeau","doi":"10.1016/j.bbalip.2025.159606","DOIUrl":"10.1016/j.bbalip.2025.159606","url":null,"abstract":"<div><div>High-density lipoproteins (HDLs) are known for their cardiovascular protection due to apolipoprotein A-1 (ApoA1), their primary protein. ApoA1 promotes cholesterol reverse transport and exhibits antioxidant and anti-inflammatory properties. Although increasing HDL levels has not consistently reduced cardiovascular mortality in clinical trials, reconstituted HDL (rHDL) nanoparticles containing ApoA1 show potential in treating acute inflammation, such as in ischemic stroke, sepsis, and even COVID-19. ApoA1 is commonly produced in bacteria due to its simplicity and potential therapeutic optimisation. Addition of a histidine tag to recombinant ApoA1 may improve purification, stability and therapeutic efficacy, although its functional impact remains a subject of debate. In this study, ApoA1 with a poly-histidine tag (His-rApoA1) was produced in a <em>clear coli</em> system for simplified purification, followed by an evaluation of the tag's effects on rHDL nanoparticle properties. rHDL and His-rHDL nanoparticles were prepared using the sodium cholate dialysis method, combining recombinant rApoA1 or His-rApoA1 with phosphatidylcholine at a 1:75 M ratio. Nuclear magnetic resonance confirmed that both forms of rApoA1 structurally resembled plasma ApoA1, whether lipid-free or in nanoparticle form. Dynamic light scattering and electron microscopy revealed nanoparticle sizes around 7 nm with native HDL-like morphology. Testing on endothelial cells (EA.hy926) showed rapid uptake of rHDL and His-rHDL while preserving cell viability. Additionally, both nanoparticles reduced interleukin-6 and ICAM-1 expression in cells, demonstrating their anti-inflammatory and protective effects, unaffected by the poly-histidine tag. Intravenous injection in mice shows homogeneous distribution of His-rHDL in the liver, lungs, and spleen, with no cytotoxicity, indicating potential use for treating inflammatory diseases.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 3","pages":"Article 159606"},"PeriodicalIF":3.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476233","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
Unveiling BCO2 function in macular pigment metabolism: Mitochondrial processing and expression in the primate retina 揭示BCO2在黄斑色素代谢中的功能:灵长类视网膜中的线粒体加工和表达
IF 3.9 2区 生物学
Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-02-18 DOI: 10.1016/j.bbalip.2025.159600
Chou Shen, Sepalika Bandara, Sanae S. Imanishi, Mahip Kalra, Yoshikazu Imanishi, Johannes von Lintig
{"title":"Unveiling BCO2 function in macular pigment metabolism: Mitochondrial processing and expression in the primate retina","authors":"Chou Shen,&nbsp;Sepalika Bandara,&nbsp;Sanae S. Imanishi,&nbsp;Mahip Kalra,&nbsp;Yoshikazu Imanishi,&nbsp;Johannes von Lintig","doi":"10.1016/j.bbalip.2025.159600","DOIUrl":"10.1016/j.bbalip.2025.159600","url":null,"abstract":"<div><div>BCO2 (β-carotene oxygenase 2) converts carotenoids into apocarotenoids by oxidative cleavage across double bonds and controls carotenoid homeostasis in vertebrate tissues. In this study, we examined BCO2's expression, localization, and activity in human cell lines and the retina. We generated peptide antibodies directed against primate BCO2 and validated their specificity using recombinant BCO1 (β-carotene oxygenase 1) and BCO2 proteins expressed in bacteria. The antibodies specifically detected human BCO2 by Western blot. In BCO2 expressing HepG2 cells, the antibodies recognized a 65 kDa mitochondrial protein that co-migrated with a recombinant truncated 522-amino-acid BCO2 variant, suggesting post-translational processing of the 579 amino acid long human BCO2 protein. Immunohistochemical analysis of macaque retina sections revealed BCO2 localization in the retinal pigment epithelium, photoreceptor inner segments, plexiform layer, and ganglion cell layer. Co-staining with COX IV indicated a mitochondrial localization of retinal BCO2 within photoreceptor inner segments. Western blot analysis of human donor retinas, separated into central and peripheral regions, identified higher BCO2 expression in the peripheral retina. Enzymatic activity assays demonstrated that BCO2 interacted with Aster proteins that transport carotenoids within cells. Our studies establish BCO2 as a mitochondrial protein expressed in the primate retina, where it likely plays a pivotal role in the metabolism of macular pigments and the maintenance of retinal health.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 3","pages":"Article 159600"},"PeriodicalIF":3.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444350","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}
引用次数: 0
Pain and functional limitations in knee osteoarthritis are reflected in the fatty acid composition of plasma extracellular vesicles 膝关节骨关节炎的疼痛和功能限制反映在血浆细胞外囊泡的脂肪酸组成中。
IF 3.9 2区 生物学
Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-02-17 DOI: 10.1016/j.bbalip.2025.159602
Anne-Mari Mustonen , Petro Julkunen , Laura Säisänen , Lauri Karttunen , Amir Esrafilian , Jusa Reijonen , Sylvain Tollis , Reijo Käkelä , Sanna P. Sihvo , Nina Höglund , Tytti Niemelä , Anna Mykkänen , Jussi Mäki , Heikki Kröger , Jari Arokoski , Petteri Nieminen
{"title":"Pain and functional limitations in knee osteoarthritis are reflected in the fatty acid composition of plasma extracellular vesicles","authors":"Anne-Mari Mustonen ,&nbsp;Petro Julkunen ,&nbsp;Laura Säisänen ,&nbsp;Lauri Karttunen ,&nbsp;Amir Esrafilian ,&nbsp;Jusa Reijonen ,&nbsp;Sylvain Tollis ,&nbsp;Reijo Käkelä ,&nbsp;Sanna P. Sihvo ,&nbsp;Nina Höglund ,&nbsp;Tytti Niemelä ,&nbsp;Anna Mykkänen ,&nbsp;Jussi Mäki ,&nbsp;Heikki Kröger ,&nbsp;Jari Arokoski ,&nbsp;Petteri Nieminen","doi":"10.1016/j.bbalip.2025.159602","DOIUrl":"10.1016/j.bbalip.2025.159602","url":null,"abstract":"<div><div>This study investigated relationships between fatty acid (FA) profiles of extracellular vesicles (EVs) and cartilage degradation, functional limitations, pain, and psychological well-being in knee osteoarthritis (KOA). Fasting plasma was collected from controls (<em>n</em> = 10), end-stage KOA patients at baseline (<em>n</em> = 12) and at 3 and 12 months (<em>n</em> = 11 and 9) after joint replacement surgery, and from KOA synovial fluid (SF) at baseline (<em>n</em> = 10). EVs were isolated with the exoEasy Maxi Kit or size-exclusion chromatography, and EV FAs were analyzed with gas chromatography–mass spectrometry. Articular cartilage loss was determined by magnetic resonance imaging, and knee pain and function were assessed through questionnaires and physiatric and neuromuscular examinations. The associations of these data with EV FA proportions were tested with the univariate analysis of variance adjusted for age and body adiposity. Higher proportions of 16:1n-7, 18:1n-7, and total monounsaturated FAs in plasma EVs were associated with less severe KOA symptoms, while higher 24:1n-9, total saturated FAs, and ratios of arachidonic acid to long-chain n-3 polyunsaturated FAs (PUFAs) were linked to KOA pain, independent of age and body adiposity. In SF EVs, higher product/precursor ratios of n-6 PUFAs were associated with increased joint stiffness, and higher total dimethyl acetals were linked to physical disability. EV FAs emerged as significant indicators of knee pain and function. The results can be utilized to discover novel biomarkers for KOA and may have implications for targeted prevention and treatment of KOA symptoms by using EVs with a specific FA cargo.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 3","pages":"Article 159602"},"PeriodicalIF":3.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456787","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
The influence of IMPDH activity on ciliogenesis and adipogenesis of 3T3-L1 cells while undergoing differentiation IMPDH活性对3T3-L1细胞分化过程中纤毛形成和脂肪形成的影响。
IF 3.9 2区 生物学
Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-02-15 DOI: 10.1016/j.bbalip.2025.159603
Kolsoom Shahdadnejad, Razieh Yazdanparast
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