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

{"title":"Methyl-end desaturases determine the capability for de novo biosynthesis of polyunsaturated fatty acids in bivalves","authors":"Naoki Kabeya ,&nbsp;Marc Ramos-Llorens ,&nbsp;Yo Nakano ,&nbsp;André Gomes-dos-Santos ,&nbsp;Amílcar Teixeira ,&nbsp;Megumu Fujibayashi ,&nbsp;Juan G. Haro ,&nbsp;Juan C. Navarro ,&nbsp;L. Filipe C. Castro ,&nbsp;Yutaka Haga ,&nbsp;Óscar Monroig","doi":"10.1016/j.bbalip.2025.159617","DOIUrl":"10.1016/j.bbalip.2025.159617","url":null,"abstract":"<div><div>Recent studies have shown that many invertebrate species possess methyl-end desaturases (herein referred to as ‘ωx’), enabling biosynthesis of polyunsaturated fatty acids (PUFA). However, the phylogenetic distribution of these enzymes across the animal kingdom remains puzzling, possibly due to horizontal gene transfer (HGT) and/or independent large-scale gene loss in certain invertebrate lineages. In molluscs, ωx genes have been identified in various cephalopods and gastropods but remain barely explored in bivalves. The increasing availability of genomic and transcriptomic resources enables a comprehensive exploration of the ωx gene repertoire in bivalves. To elucidate the distribution of ωx in bivalves, we conducted a broad homology search across existing genome and transcriptome assemblies, followed by functional characterisation of ωx in lineage representative species. Our results revealed no ωx-like sequences in any of the 65 Pteriomorphia species, suggesting gene loss in this clade. However, ωx-like sequences were found in Protobranchia, Palaeoheterodonta and Imparidentia. We analysed ωx from <em>Solemya pusilla</em> (Protobranchia), <em>Lanceolaria oxyrhyncha</em> and <em>Margaritifera margaritifera</em> (Palaeoheterodonta), and <em>Ruditapes philippinarum</em> and <em>Tridacna crocea</em> (Imparidentia). Except for <em>M. margaritifera</em>, which had two ωx genes, each species had a single ωx gene. Functional analysis showed Δ15Δ17Δ19 desaturase activity in the <em>R. philippinarum</em> and <em>T. crocea</em> ωx, while the L. <em>oxyrhyncha</em> ωx exhibited Δ15Δ17 activity but not Δ19. Both ωx from <em>M. margaritifera</em> showed no detectable activity in yeast. Interestingly, the <em>S. pusilla</em> ωx exhibited Δ12 desaturase activity. These findings highlight the diversity of ωx desaturation capabilities in bivalves, with significant gene loss in Pteriomorphia.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159617"},"PeriodicalIF":3.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881963","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":"Calpain-1 is required for abnormality of liver function and metabolism in apolipoprotein E knockout mouse evaluated noninvasively by small animal MRI and PET-CT","authors":"MOHAMED ALI AWAD ,&nbsp;Wenjiao Gu ,&nbsp;Shuangyi Li ,&nbsp;Yujie Wei ,&nbsp;Yu Tang ,&nbsp;Youming Shi ,&nbsp;HAVYARIMANA JUVENAL ,&nbsp;Ying Jiang ,&nbsp;Ting Liu ,&nbsp;Limei Shuai ,&nbsp;Zhiming Wang ,&nbsp;Bofan Wu ,&nbsp;Xiaochun Zhou ,&nbsp;Futian Tang","doi":"10.1016/j.bbalip.2025.159616","DOIUrl":"10.1016/j.bbalip.2025.159616","url":null,"abstract":"<div><div>We previously reported that calpain-1 knockout (KO) improved liver dysfunction in C57 mouse fed with high-fat diet (HFD). In the present study, Apolipoprotein E KO (ApoE KO) mouse was hybridized with calpain-1 KO mouse to obtain ApoE/calpain-1 double KO (A × C DKO) mouse to investigate role of calpain-1 in abnormality of liver function and metabolism evaluated noninvasively with MRI and PET<img>CT. Mice were divided into C57 mice fed with standard diet (C57 + SD group) and C57 + HFD, calpain-1 KO + HFD, ApoE KO + HFD and A × C DKO + HFD groups fed with HFD. Contents of albumin (ALB), activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) in serum and/or liver were measured. Fat fraction (FF) in liver was evaluated using MRI. Liver metabolism was measured using PET<img>CT after injection of ¹⁸F-Fluorodeoxyglucose (FDG). The results showed that levels of ALB, AST, ALT, TNF-α, and IL-6 in calpain-1 KO + HFD and A × C DKO + HFD mice were decreased compared with that of the matched C57 + HFD and ApoE KO + HFD mice, respectively. In addition, calpain-1 KO improved FDG metabolism in the liver. However, calpain-1 KO did not affect lipid profiles in serum and liver and FF in liver. The results suggested that calpain-1 deficiency improves dyslipidemia-induced abnormality of liver function and metabolism through inhibition of inflammation. In addition, small animal MRI and PET<img>CT are ideal approaches for noninvasively evaluating lipid deposition and substance metabolism in liver of mice.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159616"},"PeriodicalIF":3.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864417","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":"Phosphatidylinositol 4-phosphate; A minor lipid with multiple personalities","authors":"Tamas Balla","doi":"10.1016/j.bbalip.2025.159615","DOIUrl":"10.1016/j.bbalip.2025.159615","url":null,"abstract":"<div><div>Phosphorylated products of phosphatidylinositol (PI), named Diphosphoinositide (DPI) and triphosphoinositide (TPI) were identified long time ago and found to exhibit high turnover rates based on their rapid ³²P-phosphate labeling. The PI kinase activities that were responsible for their production were subsequently identified and found to be associated with different organelle membranes, including the plasma membrane. These activities were then linked with a certain group of cell surface receptors that activated phospholipase C enzymes to hydrolyze PI and used calcium or cGMP as a second messenger. This visionary concept was introduced in the seminal BBA review written by Robert Michell, exactly 50 years ago. The enzymology and functional diversity of PI 4-phosphate (PI4P) (the term that has replaced DPI) has since underwent an expansion that could not have been foreseen. In this review I will attempt to revisit this expansion with some historical reflections celebrating the 50th anniversary of the Michell review.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159615"},"PeriodicalIF":3.9,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869011","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":"Measurement of skin carotenoids and their association with diseases: a narrative review","authors":"Akira Obana","doi":"10.1016/j.bbalip.2025.159612","DOIUrl":"10.1016/j.bbalip.2025.159612","url":null,"abstract":"<div><div>Skin carotenoids are highly correlated with blood carotenoid concentrations and can be measured noninvasively using optical methods. Skin carotenoid levels are widely used in nutritional education as indicators of fruit and vegetable intake; however, research on their use as biomarkers for disease prevention is limited. This narrative review outlines methods for measuring skin carotenoid levels and describes the diseases in which the relationship between skin carotenoids and diseases has been examined, including atherosclerotic cardiovascular disease, metabolic syndrome, pediatric asthma, age-related macular degeneration, and cognitive impairment.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159612"},"PeriodicalIF":3.9,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869010","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":"Liposome of Phlorizin promote the repair of carotid atherosclerosis in rats by regulating inflammation and the Nrf2 signaling pathway","authors":"Xiaoyu Wu ,&nbsp;Chuanbo Ding ,&nbsp;Xinglong Liu ,&nbsp;Qiteng Ding ,&nbsp;Shuai Zhang ,&nbsp;Yue Wang ,&nbsp;Ting Zhao ,&nbsp;Wencong Liu","doi":"10.1016/j.bbalip.2025.159613","DOIUrl":"10.1016/j.bbalip.2025.159613","url":null,"abstract":"<div><div>Carotid atherosclerosis (CAS) is a complex cardiovascular disease linked to inflammatory response and oxidative stress. This study aimed to develop and assess the therapeutic efficacy of Phlorizin liposomes (Phlorizin-Lips) in repairing CAS in rats. Phlorizin-Lips were prepared using the film dispersion method and evaluated for controlled release, antioxidant properties, and biocompatibility. The methodology included preparing Phlorizin-Lips, conducting in vitro and in vivo experiments, observing histopathological changes in carotid arteries in a rat model, and detecting inflammatory markers and antioxidant gene expression in arterial endothelial cells using immunoblotting and ELISA. Results showed that Phlorizin-Lips significantly lowered inflammatory markers TNF-α and IL-1β in endothelial cells while upregulating Nrf2 and its downstream antioxidant genes, enhancing the cells' antioxidant capacity and reducing oxidative damage by activating the Nrf2 signaling pathway. Additionally, Phlorizin-Lips reduced carotid plaque formation, improved vascular endothelial function, and promoted CAS repair. This study underscores Phlorizin's potential as a therapeutic agent for CAS and highlights the Nrf2 pathway's role in regulating inflammation and oxidative stress. Future research will explore the clinical potential of Phlorizin-Lips.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 5","pages":"Article 159613"},"PeriodicalIF":3.9,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855761","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":"Phosphatidylethanolamine species with n-3 and n-6 fatty acids modulate macrophage lipidome and attenuate responses to LPS stimulation","authors":"Tatiana Maurício ,&nbsp;Inês M.S. Guerra ,&nbsp;Marisa Pinho ,&nbsp;Tânia Melo ,&nbsp;Stefano Bonciarelli ,&nbsp;Laura Goracci ,&nbsp;Bruno Neves ,&nbsp;Rosário Domingues ,&nbsp;Pedro Domingues","doi":"10.1016/j.bbalip.2025.159614","DOIUrl":"10.1016/j.bbalip.2025.159614","url":null,"abstract":"<div><div>Phospholipids are increasingly recognized as key regulators of biological processes, including macrophage polarization and function. Among these, phosphatidylethanolamine (PE), a major constituent of cell membranes, is pivotal in maintaining cellular structure and function, yet the mechanisms through which native PE species influence macrophage immunometabolism remain largely unexplored. This study investigates the effects of two native PE species, PE 18:0/22:6 and PE 18:0/20:4, on the lipidome of resting and LPS-activated macrophages. Using C18 HPLC-MS/MS, we identified 337 lipid molecular species across 15 lipid subclasses, 332 of which varied significantly among conditions. Both PE 18:0/22:6 and PE 18:0/20:4 supplementation modulated the macrophage lipidome without inducing a pro-inflammatory phenotype under basal conditions. Notably, supplementation with PE 18:0/22:6 and PE 18:0/20:4 significantly increased lipid classes such as PE, PE O-, SM, CL, PG, LPE and PS, producing unique lipid profiles. Pre-treatment with PE 18:0/22:6 and PE 18:0/20:4 partially attenuated LPS-induced lipidomic changes, significantly reducing lipid classes like PC, including PC O- and PC P-, and Cer, which are typically linked to inflammation. While PE 18:0/20:4, from an individual lipid species perspective, may promote certain lipid profiles compatible with pro-inflammatory signaling pathways, particularly under inflammatory conditions, PE 18:0/22:6 seems to foster a lipid profile more supportive of inflammation resolution. This behaviour of PE 18:0/22:6 and PE 18:0/20:4 highlights the intricate complexity of lipid-mediated immunomodulation and emphasizes the critical role of cellular context in determining the functional outcomes of phospholipid supplementation in macrophage lipid metabolism and immune responses.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 4","pages":"Article 159614"},"PeriodicalIF":3.9,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850486","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 synthetic TRPML1 agonist ML-SA1 mitigates intracellular lipid accumulation induced by antipsychotics in vitro by stimulating release of extracellular microvesicles","authors":"Irene Chavarría-Cubel ,&nbsp;Yessenia L. Molina ,&nbsp;Bohdan Babiy ,&nbsp;Milagros Lerma ,&nbsp;Javier Martínez-Botas ,&nbsp;Gema de la Peña ,&nbsp;María T. Vallejo ,&nbsp;Tamara Villanueva-Blanco ,&nbsp;Diego Gómez-Coronado ,&nbsp;Alberto Alcazar ,&nbsp;Miguel A. Lasunción ,&nbsp;Óscar Pastor ,&nbsp;Rebeca Busto","doi":"10.1016/j.bbalip.2025.159611","DOIUrl":"10.1016/j.bbalip.2025.159611","url":null,"abstract":"<div><div>Antipsychotics drugs disrupt lipid homeostasis by inhibiting cholesterol biosynthesis and impairing intracellular cholesterol trafficking, leading to lipid accumulation in endolysosomes. Moreover, transient receptor potential mucolipin 1 (TRPML1) cation channels of the endolysosomal membrane facilitate calcium (Ca²⁺) efflux. In the present work, we characterized the mechanism of action of the TRPML1 agonist ML-SA1 to reduce intracellular lipid accumulation and the potential to relieve the antipsychotic-induced endolysosomal lipid accumulation by enhancing the secretion of extracellular microvesicles (EVs) in Huh7 hepatocytes. We show that ML-SA1 increased the secretion of EVs, thus reducing lipid overload and lysosomal size in cells treated with clozapine or risperidone. ML-SA1 likely increased ceramide and dihydroceramide levels via ceramide synthesis <em>de novo</em>, through ML-SA1-induced upregulation of genes that code for enzymes involved in ceramide synthesis. Treatment with the Ca²⁺ chelator BAPTA-AM prevented decreased intracellular lipid accumulation and increased ceramide levels and secretion of EVs, indicating that intracellular Ca²⁺ mediated the effects of the TRPML1 agonist ML-SA1. These results show the potential of TRPML1 activation to alleviate pathological conditions characterized by accumulation of undigested substrates and overloaded dysfunctional endolysosomes.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 4","pages":"Article 159611"},"PeriodicalIF":3.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835020","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":"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}

{"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}

{"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}