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

{"title":"Molecular mechanisms of cytochrome P450-derived epoxy-fatty acids neuroprotection","authors":"Cynthia Navarro-Mabarak,&nbsp;Julio Morán","doi":"10.1016/j.bbalip.2025.159663","DOIUrl":"10.1016/j.bbalip.2025.159663","url":null,"abstract":"<div><div>The epoxyeicosatrienoic acids (EETs) are metabolites that result from the oxidation of the arachidonic acid by cytochrome P450 (CYP) epoxygenases. EETs are known to exert anti-inflammatory, antioxidant, vasodilatory, pro-angiogenic and anti-apoptotic actions. In the nervous system, EETs have been found to be neuroprotective in different models of neuronal damage. However, the molecular mechanisms responsible for these effects are not yet fully understood. This article seeks to review what is known about the signaling pathways involved in the EETs mediated neuroprotection. The mechanisms responsible for these effects are complex and involve several biological pathways that often crosstalk, including an inhibition of NFκB pathway, the activation of PPARα/γ nuclear receptors, and the activation of the PI3K/Akt pathway, among others. We also review what is known about the production and the biological significance of the epoxyeicosatrienoic acid ethanolamides (EET-EAs) and the epoxyeicosatrienoic acid glycerols (EET-EGs), metabolites that result from the epoxidation of the anandamide (AEA) and 2-arachidonylglycerol (2-AG) by CYP epoxygenases, which show endocannabinoid features.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 7","pages":"Article 159663"},"PeriodicalIF":3.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616111","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":"Endogenous synthesis of n−3 PUFAs can reduce lipid synthesis in Fad3 transgenic cattle","authors":"Danyi Li ,&nbsp;Yuxin Gao ,&nbsp;Xiaoyu Zhao ,&nbsp;Yuan Yun ,&nbsp;Chunjie Bo ,&nbsp;Lishuang Song ,&nbsp;Lei Yang ,&nbsp;Chunling Bai ,&nbsp;Guangpeng Li ,&nbsp;Guanghua Su","doi":"10.1016/j.bbalip.2025.159672","DOIUrl":"10.1016/j.bbalip.2025.159672","url":null,"abstract":"<div><div>n−3 polyunsaturated fatty acids (PUFAs) play important roles in the health, development and growth of mammals. However, most mammals, including humans, cannot synthesize n−6 and n−3 PUFAs and can only obtain them from the diet. The fatty acid desaturase 3 (<em>Fad3</em>) gene from flax encodes a fatty acid desaturase that convert n−6 PUFAs to n−3 PUFAs through desaturation at ∆15. The use of transgenic technology to produce <em>Fad3</em> transgenic cattle may be an effective way for humans to obtain n−3 PUFAs. This study utilized fibroblasts derived from <em>FAD3-</em>transgenic and wild-type (control, CON) Luxi Yellow cattle as a model system. We systematically compared differences between the two cell groups regarding endogenous gene expression, metabolite abundance, fatty acid desaturation capacity, and lipid anabolism/catabolism pathways, aiming to elucidate how endogenous n−3 PUFAs synthesized via <em>FAD3</em> regulate lipid metabolism. In <em>Fad3</em> transgenic cattle, the expression of stearoyl-CoA desaturase 5 (<em>Scd5</em>) gene was up-regulated which promote fatty acid desaturation. Endogenously PUFAs down-regulate the expression of lipid synthesis-related genes and the activity of acetyl-CoA carboxylase (ACC), up-regulate the expression of carnitine palmitoyltransferase 1 (CPT1) enzyme, reduce lipid synthesis, increase the β-oxidation of fatty acids, and thus reduce fat deposition. In summary, the <em>Fad3</em> transgenic cattle are expected to improve the nutritional value of beef, and can be used as a livestock animal model to study the beneficial effects of n−3 PUFAs.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 7","pages":"Article 159672"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724861","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":"Distinct lipidomic profiles in breast cancer cell lines relate to proliferation and EMT phenotypes.","authors":"Hanneke Leegwater, Zhengzheng Zhang, Xiaobing Zhang, Xuesong Wang, Thomas Hankemeier, Annelien J M Zweemer, Bob van de Water, Erik Danen, Menno Hoekstra, Amy C Harms, Alida Kindt, Sylvia E Le Dévédec","doi":"10.1016/j.bbalip.2025.159679","DOIUrl":"10.1016/j.bbalip.2025.159679","url":null,"abstract":"<p><p>Rewiring of lipid metabolism is a hallmark of cancer, supporting tumor growth, survival, and therapy resistance. However, lipid metabolic heterogeneity in breast cancer remains poorly understood. In this study, we systematically profiled the lipidome of 52 breast cancer cell lines using liquid chromatography-mass spectrometry to uncover lipidomic signatures associated with tumor subtype, proliferation, and epithelial-to-mesenchymal (EMT) state. A total of 806 lipid species were identified and quantified across 21 lipid classes. The main lipidomic heterogeneity was associated with the EMT state, with lower sphingolipid, phosphatidylinositol and phosphatidylethanolamine levels and higher cholesterol ester levels in aggressive mesenchymal-like cell lines compared to epithelial-like cell lines. In addition, cell lines with higher proliferation rates had lower levels of sphingomyelins and polyunsaturated fatty acid (PUFA) side chains in phospholipids. Next, changes in the lipidome over time were analyzed for three fast-proliferating mesenchymal-like cell lines MDA-MB-231, Hs578T, and HCC38. Triglycerides decreased over time, leading to a reduction in lipid droplet levels, and especially PUFA-containing triglycerides and -phospholipids decreased during proliferation. These findings underscore the role of EMT in metabolic plasticity and highlight proliferation-associated lipid dependencies that may be exploited for therapeutic intervention. In conclusion, our study reveals that EMT-driven metabolic reprogramming is a key factor in lipid heterogeneity in breast cancer, providing new insights into tumor lipid metabolism and potential metabolic vulnerabilities.</p>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":" ","pages":"159679"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788168","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":"Recombinant hirudin prevents against nonalcoholic fatty liver disease by modulating PAR1/JAK2/STAT5/STAT3/CD36 pathway","authors":"Y.U. Xiaoyu,&nbsp;Yi Sun,&nbsp;Changyuan Wang,&nbsp;Yang Wang,&nbsp;Ru Hao,&nbsp;Huijun Sun","doi":"10.1016/j.bbalip.2025.159678","DOIUrl":"10.1016/j.bbalip.2025.159678","url":null,"abstract":"<div><h3>Background</h3><div>Non-alcoholic fatty liver disease (NAFLD) has become a common liver disease. Recombinant hirudin (R-Hirudin) is an manufactured product produced by genetic engineering technology which possesses antithrombotic and hypolipidemic effects, however, the role and molecular mechanisms of R-Hirudin in NAFLD are not clear. Therefore, the aim of this study was to explore the potential mechanism of action and role of R-Hirudin in NAFLD.</div></div><div><h3>Method</h3><div>AML12 cells were induced with palmitic acid (PA) to construct an in vitro NAFLD model. C57BL/6 J male mice were continuously fed a high-fat diet (HFD) for 12 weeks to establish an in vivo NAFLD model. R-Hirudin was administered subcutaneously twice daily for 12 weeks to study the effect of R-Hirudin on NAFLD, and Vitamin E was used as a positive control. H&amp;E staining as well as ALT, AST kit were used to assess the liver injury. MASSON staining was used to assess the extent of liver fibrosis. Nile red staining, Oil red O staining and TG, TC, LDL-C, HDL-C kit were used to assess the degree of lipid droplet infiltration and lipid accumulation. LDH, MDA, SOD, GSH kit was used to assess the level of oxidative stress in vivo and in vitro. Immunofluorescence staining and western blot assay were used to assess the changes in lipid metabolism and inflammatory factor-related indices as well as target proteins in liver and cells. Chromatin immunoprecipitation analysis, dual luciferase gene reporter test and DNA pulldown assay were used to verify the relationship between STAT3, STAT5 and CD36.</div></div><div><h3>Result</h3><div>R-Hirudin significantly improved hepatic lipid accumulation, hepatic steatosis, oxidative stress and liver inflammation in the NAFLD mice. At the same time, R-Hirudin attenuated PA-induced AML12 lipid accumulation and inflammatory response. In in vitro and in vivo experiments, R-Hirudin significantly down-regulated PAR1, CD36 and p-STAT3 protein levels and up-regulated p-JAK2 and p-STAT5 protein levels. Knockdown of CD36 ameliorated lipid accumulation and inflammatory responses. In addition, PAR1 regulates the STAT5/STAT3/CD36 signaling pathway by modulating JAK2. Finally, CHIP, dual luciferase gene reporter assay, and DNA pulldown assay verified that the transcription factors STAT5 and STAT3 bind to fragments on the CD36 promoter to affect the activity of CD36.</div></div><div><h3>Conclusion</h3><div>The results indicated that R-Hirudin might ameliorate steatosis, lipid accumulation and inflammatory response through PAR1/JAK2/STAT5/STAT3/CD36 signaling pathway and thus alleviate NAFLD.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 7","pages":"Article 159678"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768262","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":"Phosphoinositides as regulators of membrane contact sites","authors":"Håvard S. Haukaas ,&nbsp;Harald Stenmark","doi":"10.1016/j.bbalip.2025.159673","DOIUrl":"10.1016/j.bbalip.2025.159673","url":null,"abstract":"<div><div>Membrane contact sites (MCSs) between the different compartments of the cell play important roles in lipid, protein and ion transfer. Phosphoinositides are crucial for the functions of many MCSs, either as membrane anchors for MCS proteins, or as part of a countertransport mechanism driven by phosphoinositide dephosphorylation in the endoplasmic reticulum. Here we review the involvement of phosphoinositides in MCSs between the endoplasmic reticulum and other organelles such as the plasma membrane, mitochondria, endosomes, lysosomes, autophagosomes and the Golgi complex. These phosphoinositide-containing MCSs mediate transfer of Ca2+, phospholipids, cholesterol, and a motor protein, and thus are of great importance for cellular physiology.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 7","pages":"Article 159673"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727158","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":"Acetyl-CoA acyltransferase 2 as a metabolic modulator: Unraveling its impact on hepatic lipid dynamics in chicken embryos","authors":"Mengling Peng ,&nbsp;Luyao Kan ,&nbsp;Xinyu Zhao ,&nbsp;Chang Liu ,&nbsp;Wenye Hu ,&nbsp;Yiting Tang ,&nbsp;Yuhan Meng ,&nbsp;Mengran Sun ,&nbsp;Juhua Wang ,&nbsp;Fugui Fang ,&nbsp;Jie Zhou","doi":"10.1016/j.bbalip.2025.159674","DOIUrl":"10.1016/j.bbalip.2025.159674","url":null,"abstract":"<div><div>Despite the established role of acetyl-CoA acyltransferase 2 (ACAA2) in hepatic lipid homeostasis in mammals, its function in regulating hepatic lipid metabolism during the embryonic stage of chickens remains unexplored. This study aimed to explore the regulatory role of ACAA2 in hepatic lipid metabolism and investigate its molecular mechanisms in chicken embryos. A recombinant ACAA2-shRNA plasmid was successfully constructed for targeted suppression of ACAA2 expression. Knockdown of ACAA2 significantly increased triglyceride content, promoted lipid droplet accumulation, and upregulated lipogenesis-related gene expression in chicken embryos. The knockdown of ACAA2 significantly suppressed both mRNA and protein expression of peroxisome proliferator-activated receptor α (PPARα) and carnitine palmitoyl transferase 1 (CPT1), while conversely upregulating sterol regulatory element binding protein-1c (SREBP-1c) mRNA and protein expression. Notably, these metabolic alterations caused by ACAA2 knockdown were markedly reversed by the activation of PPARα in primary chicken embryonic hepatocytes, suggesting functional crosstalk between the ACAA2 and PPARα signaling pathways. These results indicate that fat accumulation action of the knockdown of ACAA2 was due to enhancing SREBP-1c expression and reducing PPARα expression. In present study, ACAA2 was identified as a critical modulator of embryonic lipid metabolism, offering a target for interventions to reduce embryonic mortality or metabolic diseases in poultry.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 7","pages":"Article 159674"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144739426","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":"Galectin-3 gene deletion alters lipid profile in healthy and cardiomyopathy mouse hearts","authors":"Xiao-Jun Du ,&nbsp;Kevin Huynh ,&nbsp;Mark Ziemann ,&nbsp;Gang She ,&nbsp;Wei Wu ,&nbsp;Thy Duong ,&nbsp;Xia-Xia Hai ,&nbsp;Yi-Yi Yang ,&nbsp;Wei-Bo Zhao ,&nbsp;Qun Lu ,&nbsp;Yi Zhang ,&nbsp;Xiu-Ling Deng ,&nbsp;Peter J. Meikle","doi":"10.1016/j.bbalip.2025.159676","DOIUrl":"10.1016/j.bbalip.2025.159676","url":null,"abstract":"<div><div>Galectin-3 (Gal3) is known to interact with glycans of proteins and lipids. In cardiovascular disease, the elevated expression of Gal3 mediates inflammation, hypertrophy and fibrosis. We explored the effect of Gal3 on the cardiac lipid profile in healthy mice or in mice with dilated cardiomyopathy (DCM). Using lipidomics and gene-targeted mouse models, we studied the influence of Gal3 gene deletion on cardiac lipid profiles in the healthy mice or mice with DCM. Cardiac-restricted transgenic activation of Hippo pathway led to DCM phenotype and Gal3 upregulation. DCM mice were cross-bred with Gal3 gene knockout (KO) mice to obtain genotypes of non-transgenic (nTG), Gal3-KO, DCM and DCM/KO. Alterations in the lipid classes and species due to Gal3-KO were identified by lipidomics in hearts from mice of four genotypes. In the nTG background, Gal3-KO increased ether lipids and lysophospholipids, and induced diverse changes of sphingolipid subclasses. The DCM hearts exhibited profound lipidomic changes including increase in sphingolipids and reduction in ether lipids and triglycerides, which were partially reversed by Gal3 deletion. We demonstrated the nuclear and mitochondrial localization of Gal-3 in DCM hearts. Transcriptomics revealed that Gal3 deletion in the DCM background partially restored the suppressed expression of mitochondrial lipid metabolic genes. In conclusion, we report multiple alterations in the lipid classes and species in the heart by Gal3 deletion in the healthy mice and, more importantly mice with DCM background. Our findings suggest that Gal3 alters cardiac contents of lipids in the DCM model in part through suppression of mitochondrial metabolism.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 7","pages":"Article 159676"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144771305","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":"ABCA1 modifies plasma membrane organization of living cells","authors":"Mateusz Kondratowicz ,&nbsp;Ambroise Wu ,&nbsp;Ewa Grela ,&nbsp;Olga Raducka-Jaszul ,&nbsp;Rafał Luchowski ,&nbsp;Ewa Błaszczak ,&nbsp;Karolina Wójtowicz ,&nbsp;Yannick Hamon ,&nbsp;Wiesław I. Gruszecki ,&nbsp;Katarzyna Cieślik-Boczula ,&nbsp;Tomasz Trombik","doi":"10.1016/j.bbalip.2025.159667","DOIUrl":"10.1016/j.bbalip.2025.159667","url":null,"abstract":"<div><div>The plasma membrane, composed mostly of lipids and proteins, is a dynamic structure essential for maintaining cellular homeostasis and signaling. Its composition, organization and molecular dynamics have important functional consequences for the cell, while aberrations of its integrity are associated with various human pathologies, including cancers, inflammatory and neurodegenerative diseases. ATP-binding cassette transporter A1 (ABCA1) plays a key role in cellular lipid and cholesterol metabolism, yet its impact on plasma membrane organization and dynamics remains incompletely understood. Using multidisciplinary approaches, we investigated how ABCA1 activity alters plasma membrane dynamics and nanodomain organization in living cells. Fluorescence lifetime imaging microscopy (FLIM) and fluorescence anisotropy showed that active ABCA1 increases membrane homogeneity. Proton nuclear magnetic resonance (¹H NMR) spectroscopy of living cells demonstrated that ABCA1 activity alters membrane fluidity and induces its distinct chemical composition changes. Furthermore, spot variation fluorescence correlation spectroscopy (svFCS) revealed that ABCA1 modulates lipid and protein diffusion dynamics. Our findings confirm and extend previous studies by demonstrating that ABCA1 is one of the key regulators of plasma membrane lipid distribution, influencing its structural and functional organization. By modulating lipid-raft nanodomains, ABCA1 activity may have broader implications for membrane-dependent cellular processes.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 7","pages":"Article 159667"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The influence of soluble epoxide hydrolase inhibition and their PUFA-derived epoxides in osteoblast bone metabolism: an in vitro study","authors":"Duilio Benicio e Silva-Junior ,&nbsp;Ney Robson Bezerra Ribeiro ,&nbsp;David Martins Nunes Junior ,&nbsp;Lucas Fernando Presa Tardivo ,&nbsp;Rodrigo Chaves Peixoto ,&nbsp;Lucas Novaes Teixeira ,&nbsp;Bruce D. Hammock ,&nbsp;Juliana Trindade Clemente-Napimoga ,&nbsp;Marcelo Henrique Napimoga ,&nbsp;Henrique Ballassini Abdalla","doi":"10.1016/j.bbalip.2025.159669","DOIUrl":"10.1016/j.bbalip.2025.159669","url":null,"abstract":"<div><div>EpFAs are crucial mediators in resolving inflammation and regulating various biological processes. However, their activity is constrained by the rapid metabolism mediated by the soluble epoxide hydrolase (sEH), which converts EpFAs into inactive or even pro-inflammatory diols. Nevertheless, the specific effects of soluble epoxide hydrolase inhibition (sEHI) and EpFAs on osteogenic cell metabolism remain unclear. Cultures of the human immortalized osteoblast-like cell line (SAOS-2) were treated with varying concentrations (0.1–10 μM) of the potent sEHI TPPU or EpFAs (epoxyeicosatrienoic acids [EETs], epoxydocosapentaenoic acids [EDPs], and epoxyeicosatetraenoic acids [EEQs], derived from arachidonic acid [ARA], eicosapentaenoic acid [EPA], and docosahexaenoic acid [DHA], respectively). Cellular metabolic activity and proliferation were evaluated. Osteogenic potential was assessed through alkaline phosphatase activity, mineral nodule formation, and the expression of osteogenic markers, including Runx-2, Osx, Col1, Bsp, Opg, Ocn, Opn, and sEH. Treatment with TPPU and EpFAs enhanced cellular metabolic activity during the first 48 h without affecting proliferation. Alkaline phosphatase activity and mineral nodule formation assays revealed that TPPU significantly stimulated osteogenic differentiation, while EpFAs, particularly EETs, EEQs, and EDPs, promoted osteogenesis predominantly at later stages. Furthermore, TPPU modulated the expression of key osteogenic markers, enhancing differentiation. Notably, EDPs were found to disrupt the synergistic effects between sEHI and EpFAs during the mineralization process. These findings suggest that sEHI enhances mineralization and may facilitate tissue regeneration in vitro. The differential effects of EpFAs and their interplay with sEHI provide insights into potential therapeutic strategies for bone tissue engineering and regeneration.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 7","pages":"Article 159669"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768263","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":"Metformin promotes lipid droplet-mitochondria coupling and improves insulin secretion in pancreatic β-cells exposed to lipotoxicity","authors":"Aneta M. Dobosz ,&nbsp;Ewelina Krogulec ,&nbsp;Nataniel Stefanowski ,&nbsp;Maria Kendziorek ,&nbsp;Magdalena Lebiedzinska-Arciszewska ,&nbsp;Mariusz R. Wieckowski ,&nbsp;Justyna Janikiewicz ,&nbsp;Agnieszka Dobrzyn","doi":"10.1016/j.bbalip.2025.159664","DOIUrl":"10.1016/j.bbalip.2025.159664","url":null,"abstract":"<div><div>Lipotoxicity that is caused by excess lipid accumulation is a major factor that contributes to gradual impairments of β-cell function and the development of type 2 diabetes. Metformin has shown protective effects against lipid-induced damage in β-cells, but its specific mechanisms of action within pancreatic islets remain unclear. The present study comprehensively examined direct effects of metformin on lipid metabolism pathways in INS-1E β-cells that were exposed to lipotoxic stress. Our results showed that metformin reduced both the number and size of lipid droplets in palmitate-treated INS-1E cells. This was followed by an increase in fatty acid utilization and the enhanced association between mitochondria and lipid droplets. Under conditions of palmitate overexposure, metformin limited the activity of adipose triglyceride lipase and lipogenic regulators, such as stearoyl-CoA desaturase, and suppressed fatty acid uptake into cells. Additionally, metformin alleviated triglyceride and free fatty acid accumulation and partially reversed palmitate-induced impairments in insulin secretion in INS-1E cells that were subjected to lipotoxicity. Notably, this beneficial effect of metformin on insulin secretion in INS-1E cells exposed to lipotoxic stress was less pronounced when the balance between mitochondrial fusion and fission was disturbed. These findings provide additional mechanistic insights into pleiotropic effects of metformin and its role in regulating β-cell function.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 7","pages":"Article 159664"},"PeriodicalIF":3.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636022","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}