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

{"title":"Modulation of lipid droplet biogenesis by p38 MAPK and caspase-1 in docosahexaenoic acid-induced EA.hy926 endothelial cell apoptosis","authors":"Youjia Du ,&nbsp;Xucheng Lv ,&nbsp;Yan Shen ,&nbsp;Xiaoou Ren ,&nbsp;Shoudong Ye","doi":"10.1016/j.bbalip.2025.159683","DOIUrl":"10.1016/j.bbalip.2025.159683","url":null,"abstract":"<div><div>Endothelial cells form a single layer of endothelium that lines the inner surface of the blood vessels. Healthy endothelial cells play important roles in the maintenance of the circulation homeostasis, while endothelial cell apoptosis has been implicated in the pathology of cardiovascular diseases. Lipid droplets (LDs) are multifunctional organelles that can be formed in endothelial cells during various fatty acid-induced apoptosis. However, the role of LDs in endothelial cell apoptosis and the mechanism of action have received limited attention. Our previous study showed that docosahexaenoic acid (DHA) induces endothelial cell apoptosis through the activation of mitogen-activated kinases (MAPKs) and caspases, and suggested a critical role of p38 MAPK and unknown caspases other than caspase-8, -9, and -3 in the modulation of apoptosis. Therefore, the current study is to investigate the regulatory mechanism of lipid droplet biogenesis by p38 MAPK and caspase-1 in DHA-induced EA.hy926 endothelial cell apoptosis. Our results showed that p38 MAPK and caspase-1 formed a positive feedback loop in upregulating LD biogenesis. Inhibiting the formation of LDs through diacylglycerol acyltransferases suppression but not caspase-1 inhibition led to an alleviation of cell apoptosis. Inhibition of LD biogenesis also negatively impacted the activation of p38 MAPK and caspase-1. Our study suggested a role of the interaction between p38 MAPK and caspase-1 in the modulation of LD biogenesis and apoptosis in DHA-treated endothelial cells, and revealed a potential role of LD in the modulation of the signal transduction involving p38 MAPK and caspase-1.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 8","pages":"Article 159683"},"PeriodicalIF":3.3,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902570","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":"Echinacoside suppresses macrophage lipid accumulation and attenuates atherosclerosis via the MDM2/PPARγ/ABCA1 signaling axis","authors":"Qin-Yi Zhou ,&nbsp;Jing Zhou ,&nbsp;Zhao-Bing Li ,&nbsp;Qun Wang ,&nbsp;Duo Gong ,&nbsp;Wang Liu ,&nbsp;Chao-Ke Tang","doi":"10.1016/j.bbalip.2025.159681","DOIUrl":"10.1016/j.bbalip.2025.159681","url":null,"abstract":"<div><div>Macrophage cholesterol efflux, a critical step in reverse cholesterol transport, plays a pivotal role in the attenuation of atherosclerosis. Echinacoside, a natural compound with anti-inflammatory, antioxidant, and antitumor properties, has emerged as a potential therapeutic agent for atherosclerosis. However, the mechanisms underlying its anti-atherosclerotic effects remain unclear. In this study, we aimed to investigate the effects of echinacoside on lipid accumulation in macrophage-derived foam cells and on atherosclerotic progression in apoE^−/− mice. Our key findings indicated that echinacoside upregulated ABCA1 expression, enhanced macrophage cholesterol efflux, and reduced lipid accumulation by modulating MDM2/PPARγ signaling. Additionally, echinacoside alleviated atherosclerotic progression in high-fat diet-fed apoE^−/− mice. MDM2 overexpression with pcDNA3.1-MDM2 eliminated the effects of echinacoside on ABCA1 and PPARγ upregulation, macrophage cholesterol efflux, and lipid accumulation. In conclusion, echinacoside inhibits macrophage lipid accumulation and alleviates atherosclerotic progression via the MDM2/PPARγ/ABCA1 signaling pathway.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 7","pages":"Article 159681"},"PeriodicalIF":3.3,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863571","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":"Lipid metabolic adaptations of multi-donor mesenchymal stem cells during osteodifferentiation","authors":"Daniela S.C. Bispo,&nbsp;Inês C.R. Graça,&nbsp;Catarina S.H. Jesus,&nbsp;João E. Rodrigues,&nbsp;Brian J. Goodfellow,&nbsp;Mariana B. Oliveira,&nbsp;João F. Mano ,&nbsp;Ana M. Gil","doi":"10.1016/j.bbalip.2025.159680","DOIUrl":"10.1016/j.bbalip.2025.159680","url":null,"abstract":"<div><div>Mesenchymal stem cell (MSC) osteodifferentiation is accompanied by important lipid metabolic adaptations, which may reveal relevant biomarkers and potential osteoinductive species. However, high donor variability remains a challenge for biomarker identification. This work unveiled shared lipid features of human adipose-tissue MSC (hAMSC) for three independent donors, using an untargeted NMR spectroscopy methodology. The results showed that osteodifferentiation induced increases in esterified cholesterol preferentially enriched in shorter monounsaturated fatty acids (MUFA), and triacylglycerides containing longer fatty acids (FA), both consistent with increased lipid droplet formation in the cytosol. Membrane adaptations involved hydrolysis of phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn), possibly to allow subsequent polyunsaturated FA incorporation (to enhance membrane fluidity) and facilitate removal of peroxidized FA, while originating inorganic phosphate (Pi) for mineralization. PtdCho levels seem closely linked to the creatine-phosphocreatine axis, reflecting a shared contribution to Pi generation. MUFA also appeared to serve as preferential substrates for <em>β-</em>oxidation, apparently in association with antioxidative mechanisms. The above metabolic effects were indicative of a common pathway modulation in the three donors, with predicted upregulation of ALP, collagen, antioxidant enzymes, LDL, and HSP27, and downregulation of ERK 1/2 (notably upregulated at day 7), arginase, and vacuolar H⁺-ATPase. Notably, the proposed donor-independent lipid signature enabled the detection of osteodifferentiating cells with nearly 90 % accuracy, highlighting the complex interplay among different lipid families, with esterified cholesterol, triacylglycerides, and phospholipids emerging as main players in osteodifferentiation.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 7","pages":"Article 159680"},"PeriodicalIF":3.3,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811669","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":"2025-08-05","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":"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":"2025-07-31","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":"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":"2025-07-31","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":"The individual isoforms of ORMDL, the regulatory subunit of serine palmitoyltransferase, have distinctive sensitivities to ceramide","authors":"Usha Mahawar ,&nbsp;Deanna L. Davis ,&nbsp;Muthukumar Kannan ,&nbsp;John Suemitsu ,&nbsp;Christopher D. Oltorik ,&nbsp;Faheem Farooq ,&nbsp;Raheema Fulani ,&nbsp;Collin Weintraub ,&nbsp;Binks Wattenberg","doi":"10.1016/j.bbalip.2025.159677","DOIUrl":"10.1016/j.bbalip.2025.159677","url":null,"abstract":"<div><div>Sphingolipids play crucial roles in cell membrane structure and in multiple signaling pathways. Sphingolipid de novo biosynthesis is mediated by the serine palmitoyltransferase (SPT) enzyme complex. Homeostatic regulation of this complex is dependent on its regulatory subunit, the ORMDLs, of which there are three isoforms. It is well established that the ORMDLs regulate SPT activity, but it is still unclear whether the three ORMDL isoforms have distinct functions and properties. Here, we focus on understanding the physiological importance of ORMDL isoforms (ORMDL1, ORMDL2, and ORMDL3) in regulating SPT activity and sphingolipid levels. This study delves into the differential responses of the SPT complexes containing different ORMDL isoforms to cellular ceramide levels. By using the CRISPR/Cas9 gene editing tool, we have developed Hela cell lines each of which harbor only one of the three ORMDL isoforms as well as a cell line deleted for all three isoforms. Consistent with other studies, we find that deletion of all three ORMDL isoforms desensitizes SPT to ceramide and dramatically increases levels of cellular sphingolipids. In contrast, each ORMDL isoform alone is capable of regulating SPT activity and maintaining normal levels of sphingolipid. Strikingly, however, we find that each ORMDL isoform exhibits isoform-specific sensitivity to ceramide. This suggests that the inclusion of specific ORMDL isoforms into the SPT complex may accomplish a fine-tuning of sphingolipid homeostasis. The study not only emphasizes the need for further investigation into the distinct roles of ORMDL isoforms but also sheds light on their potential as therapeutic targets.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 7","pages":"Article 159677"},"PeriodicalIF":3.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759034","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":"Androgen regulates seasonal changes in triglyceride synthesis through the AR-SREBP1-FASN axis in the scented glands of muskrats (Ondatra zibethicus)","authors":"Xinjing Shi ,&nbsp;Qingjing Gao ,&nbsp;Wenjing Lu ,&nbsp;Yuning Xie ,&nbsp;Haolin Zhang ,&nbsp;Dong Zhang ,&nbsp;Yuning Liu ,&nbsp;Qiang Weng","doi":"10.1016/j.bbalip.2025.159675","DOIUrl":"10.1016/j.bbalip.2025.159675","url":null,"abstract":"<div><div>SREBP1 (sterol regulatory element binding protein 1) plays an important role in maintaining lipid balance in mammals. Previous research showed that androgen significantly regulated the secretion of lipid-rich musky odor substances from the scented glands of muskrats. Our investigation provides insights into the pathways through which androgen induces SREBP1 expression and affects seasonal changes in triglyceride synthesis in muskrat scented glands. During the breeding season, pronounced Oil Red O staining was confirmed in the scented glandular tissues, and transmission electron microscopy displayed a marked increase in lipid droplets. The scented glands exhibited a higher triglyceride content, which coincided with augmented circulating testosterone, dihydrotestosterone, as well as increased scented glandular testosterone and dihydrotestosterone concentrations. Transcriptomic, proteomic and metabolomic analyses of the scented glands revealed associations with fatty acid biosynthesis, while plasma metabolomic data indicated an increase in metabolites serving as precursors during the breeding season for de novo fatty acid synthesis. Expression levels of genes and proteins related to lipid synthesis and lipid droplets, as well as FASN activity, were significantly elevated in the breeding season. Immunolocalization studies demonstrated the presence of these proteins in glandular and epithelial cells in both seasons. Moreover, in vitro treatment of the scented glandular cells with testosterone resulted in elevated expressions of triglyceride synthesis-related genes. These findings suggested that androgen modulates triglyceride synthesis to enhance lipid droplet formation via the AR-SREBP1-FASN Axis in the scented glands of muskrats, thereby shedding light on the hormonal regulation of lipid metabolism in seasonal breeders.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 7","pages":"Article 159675"},"PeriodicalIF":3.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724860","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":"2025-07-28","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":"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":"2025-07-28","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}