Lipids最新文献

{"title":"CerS2 Overexpression Enhances Palmitoyl-CoA-Induced Cytotoxicity and Alters Ceramide Species Composition in Breast Cancer Cells.","authors":"Senem Ece Üner, Bürke Çırçırlı, Mutay Aslan","doi":"10.1002/lipd.70071","DOIUrl":"https://doi.org/10.1002/lipd.70071","url":null,"abstract":"<p><p>Sphingolipid metabolism, particularly the balance between pro-apoptotic ceramide and pro-survival sphingosine-1-phosphate (S1P), has been associated with breast cancer progression. The aim of the present study was to examine whether ceramide synthase 2 (CerS2) overexpression is associated with changes in increased palmitoyl-CoA (PCA) based ceramide buildup and cell fate changes in MCF-7 breast cancer cells, a hormone receptor-positive model. CERS2 plasmid transfected cells were treated with PCA and/or the CerS inhibitor, fumonisin B1 (FB1). Cell viability, the proliferation marker proliferating cell nuclear antigen (PCNA), apoptosis (TUNEL and cleaved caspase-3), and sphingolipid profiles were evaluated. High-dose PCA (100 μM) significantly reduced MTT signal and PCNA expression and increased apoptotic markers, with stronger effects in CerS2-overexpressing cells. Across short- and longer-term exposures, the response pattern was concentration- and time-responsive but not uniformly monotonic. Lipidomic analysis revealed that PCA and CerS2 overexpression increased C16 ceramide and very-long-chain ceramides (C22-C24), respectively. FB1 decreased the level of ceramide, elevated S1P and partly counteracted PCA-induced cytotoxicity. FB1 pre-treatment which was applied sequentially restricted but did not eliminate apoptosis. These findings indicate that CerS2 overexpression reshapes the cellular response to substrate-driven sphingolipid stress by altering acyl-chain-specific ceramide composition and the balance between ceramide- and S1P-associated signaling. Rather than reflecting isolated pathway effects, the results support a context-dependent role for CerS2 in modulating apoptotic sensitivity in MCF-7 breast cancer cells.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral Delivery of Tocotrienols: Addressing Pharmacokinetic Challenges With Formulation-Based Strategies.","authors":"An Gie Ooi, Kah Hay Yuen, Chee Chin Chu, Jia Woei Wong","doi":"10.1002/lipd.70069","DOIUrl":"https://doi.org/10.1002/lipd.70069","url":null,"abstract":"<p><p>Tocotrienols (T3), vitamin E analogues with potent antioxidant and therapeutic properties, have attracted increasing scientific interest. However, their clinical translation is hindered by poor and variable oral bioavailability. This limitation arises from their low aqueous solubility, rapid elimination, chemical instability and weak affinity for α-tocopherol transfer protein, which restricts systemic retention and tissue distribution. The intestinal absorption of T3 is a saturable, concentration-dependent process mediated primarily by Niemann-Pick C1-like 1 and, to a lesser extent, scavenger receptor class B type 1. This review outlines the pharmacokinetics of T3 and critically examines recent advances in oral delivery systems aimed at improving bioavailability. While existing approaches offer improvement in bioavailability, intrinsic absorption barriers remain a challenge. Future progress requires integrating both physicochemical and biological strategies, focusing on modulating intestinal transporters and controlling the release kinetics to mitigate local saturation. Such next-generation formulations may enable consistent absorption, prolonged circulation, and enhanced therapeutic efficacy of T3.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148272224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Very Low Cholesterol Non-Cardiovascular Risks: A Critical Appraisal and Framework for Individualized Management.","authors":"Alberto Boretti","doi":"10.1002/lipd.70068","DOIUrl":"https://doi.org/10.1002/lipd.70068","url":null,"abstract":"<p><p>Randomized trial evidence firmly establishes that lowering LDL-C reduces atherosclerotic cardiovascular disease. However, observational studies consistently report U-shaped cholesterol-mortality associations, raising concerns about potential non-cardiovascular risks at very low levels. This narrative review (not systematic review; no PRISMA flow or formal search strategy) distinguishes observational associations from causal evidence, defines \"very low cholesterol\" as LDL-C < 70 mg/dL, and emphasizes patient context in personalized management for adults (not pediatrics). Epidemiologically, low cholesterol correlates with cancer, depression, hemorrhagic stroke, and infection, with biological plausibility involving membrane integrity, neurosteroid synthesis, vascular stability, and immune function. Yet these mechanisms remain speculative, and such associations are highly susceptible to reverse causation, whereby chronic illness itself lowers cholesterol. Critically, Mendelian randomization studies and meta-analyses of randomized controlled trials-including statin and PCSK9 inhibitor trials-have not demonstrated causal links between pharmacologically induced low LDL-C and these adverse outcomes. Mathematical models (quadratic, hormetic, biomechanical) are included as conceptual illustrations only and are not clinically validated. All mathematical models (quadratic, hormetic, Arrhenius, Hill, Laplace, CHI) presented herein are conceptual illustrations only, not clinically validated. They serve heuristic and hypothesis-generating purposes, not clinical prediction. For most high-risk patients, cardiovascular benefits clearly outweigh theoretical risks. However, subgroups such as the very elderly, frail individuals, or those with prior hemorrhagic stroke warrant individualized assessment guided by comorbidities, life expectancy, and treatment safety rather than cholesterol levels alone. Ultimately, observational signals do not challenge established LDL-C reduction benefits in high-risk populations; their primary value lies in reinforcing context-driven personalization at the margins of therapy.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exometabolomics Reveals Metabolic Modulation Induced by Chia Oil Supplementation in Adipose Tissue Explants From Obese Mice.","authors":"Gilson Costa Dos Santos, Agatha Assis-Ferreira, Gabrielly Muniz-Cassuce, Tatiana El Bacha, Christina Barja-Fidalgo, Simone Vargas da Silva","doi":"10.1002/lipd.70066","DOIUrl":"https://doi.org/10.1002/lipd.70066","url":null,"abstract":"<p><p>Obesity impairs adipose tissue metabolism and dietary interventions capable of modulating these alterations remain insufficiently explored. To investigate depot-specific metabolic adaptations in subcutaneous (SAT) and epididymal adipose tissue (EAT) in response to chia oil supplementation. Male C57BL/6J mice received a control diet (C group) or a high-fat diet (H group) for 8 weeks, followed by 5 weeks of chia oil supplementation (1.5% w/w; 1.5 g/100 g diet; CC and HC groups). Exometabolomic profiling of SAT and EAT explants was performed using ¹H-NMR, accompanied by targeted gene-expression analyses. Chia oil supplementation reduced adipocyte hypertrophy and improved glucose tolerance in obese mice without altering body or adipose tissue mass. Obesity markedly decreased l-histidine secretion in SAT and this effect was not modified by chia oil supplementation. In obese SAT, chia oil reduced l-valine and l-proline secretion and increased l-threonine levels, while it increased lactate secretion in obese EAT. Obesity did not significantly affect acetate secretion, although chia oil supplementation resulted in a depot-specific variation exclusively in the HC group. Correlation analysis revealed that chia oil modified metabolic interaction networks in both adipose depots. Chia oil supplementation induced depot-specific metabolic adjustments in SAT and EAT, highlighting the plasticity of adipose tissue and the potential of dietary lipids to modulate adipose metabolic networks.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"61 3","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148067260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Pharmacology Insights Into Statin-Induced Coenzyme Q10 Deficiency: Lipid Metabolic Crosstalk, TNF-MAPK Signaling, and Muscle Toxicity.","authors":"Nila Ganamurali, Sarvesh Sabarathinam","doi":"10.1002/lipd.70028","DOIUrl":"10.1002/lipd.70028","url":null,"abstract":"<p><p>This in silico network-pharmacology investigation delineates the molecular interplay linking statin-induced Coenzyme Q10 (CoQ10) deficiency to statin-associated muscle symptoms (SAMS). GeneCards-derived targets related to SAMS, CoQ10 deficiency, and statins were integrated, and the intersecting gene set was analyzed through STRING-based protein-protein interaction mapping, followed by hub-gene prioritization using CytoHubba. Functional enrichment via ShinyGO revealed that the 145 common genes converge predominantly on inflammatory, metabolic, and mitochondrial pathways. Tumor necrosis factor (TNF) emerged as a principal regulatory node, exerting influence through Mitogen-Activated Protein Kinase (MAPK)-mediated apoptotic and stress-response cascades that plausibly contribute to mitochondrial dysfunction, oxidative stress, impaired energy metabolism, and myocellular injury in the context of CoQ10 depletion. The constructed pathway-based interaction network illustrates how suppression of the mevalonate pathway by statins disrupts CoQ10 biosynthesis, sensitizing muscle tissue to cytokine-driven inflammatory signaling and amplifying apoptotic susceptibility. Collectively, the findings highlight the TNF-MAPK axis as a mechanistic core of SAMS pathophysiology and underscore the interconnected roles of immune activation, lipid metabolic imbalance, and mitochondrial impairment. These insights provide a molecular rationale for therapeutic strategies targeting mitochondrial preservation or inflammatory modulation, including CoQ10 supplementation, and reinforce the need for experimental and clinical validation to substantiate computationally derived predictions.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":" ","pages":"299-307"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145714588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of CYP2C19 Genotype Variants on PCSK9 Inhibitor Efficacy in Lipid-Lowering Among Patients With Symptomatic Intracranial Atherosclerotic Stenosis.","authors":"Chao Zhao, Nuan Wang, Di Shi, Hao Zhou, Dan Chen, Guofang Chen","doi":"10.1002/lipd.70018","DOIUrl":"10.1002/lipd.70018","url":null,"abstract":"<p><p>Ischemic stroke is frequently associated with symptomatic intracranial atherosclerotic stenosis (sICAS), is a leading cause of global disability and mortality. Current guidelines recommend dual antiplatelet and intensive statin therapies. Proprotein convertase subtilisin 9/kexin type 9 (PCSK9) inhibitors have emerged as a potent lipid-lowering therapy, potentially influenced by genetic variations, particularly in the CYP2C19 gene. This study at Xuzhou Central Hospital from January 2021 to December 2023 included 151 patients divided into a statin group (n = 73) and a PCSK9 inhibitor (PCSK9i) group (n = 78). It evaluated lipid profiles, inflammatory markers, neurological function, and clinical outcomes over a 180-day follow-up period, with additional analysis stratified by CYP2C19 genotype. The PCSK9i group demonstrated significant improvements in lipid parameters compared to the statin group, including greater reductions in low-density lipoprotein cholesterol (LDL-C) (p = 0.008), total cholesterol (TC) (p < 0.001), and triacylglycerols (TAG) (p = 0.041), along with apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) (both p < 0.001). Inflammatory markers, particularly interleukin-6 (IL-6), significantly reduced in the PCSK9i group (p < 0.001). In the PCSK9i group, CYP2C19 rapid metabolizers achieved greater reductions in LDL-C (p = 0.021), ApoB (p = 0.003), and IL-6 levels (p = 0.041) compared to slow metabolizers. Post-treatment modified Rankin Scale (mRS) scores were significantly lower in rapid metabolizers compared to slow metabolizers (p = 0.018), though clinical events occurred infrequently in both subgroups. This study demonstrates that PCSK9 inhibitor therapy combined with statins provides enhanced lipid-lowering and anti-inflammatory effects compared to statin monotherapy in sICAS patients. While the CYP2C19 genotype may influence specific treatment responses, particularly lipid parameters, its impact on clinical outcomes requires further investigation.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":" ","pages":"319-329"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eicosapentaenoic and Docosahexaenoic Acid Levels in Mouse Tissues After Intake of Echium and Ahiflower Oils Rich in Stearidonic and α-Linolenic Acids.","authors":"Letícia V Segre, Mariana S Bisinotto, Inar A Castro","doi":"10.1002/lipd.70041","DOIUrl":"10.1002/lipd.70041","url":null,"abstract":"<p><p>Omega-3 fatty acids (n-3 FA), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been consumed aiming to reduce cardiovascular disease. Fish oil is the main dietary source of EPA and DHA but has limitations that have stimulated interest in sustainable alternatives such as Echium ( Echium plantagineum ) and Ahiflower ( Buglossoides arvensis ) oils, both rich in α-linolenic acid (ALA) and stearidonic acid (SDA), precursors of EPA. However, the ability of these two oils to increase EPA and DHA levels in different tissues remains unclear. Thus, this study aimed to investigate the effects of SDA-rich oils on fatty acid profiles in different biological matrices of C57BL/6 mice. Animals received diets supplemented with soybean oil (control), Echium oil, or Ahiflower oil (4% diet) for 8 weeks, providing n-3/n-6 FA intake ratios of 0.14, 1.51, and 2.28, respectively. Fatty acids were analyzed in plasma, erythrocytes, liver, adipose tissue, heart, and brain. Both SDA-rich oils significantly increased EPA levels across all tissues in a dose-dependent manner compared with the control, whereas changes in DHA were limited and tissue-specific. Despite the increase in EPA, DHA levels remained unchanged in the heart, brain, and plasma. In erythrocytes, DHA levels were higher in both SDA-rich oil groups compared with the control. Echium and Ahiflower oils may be strategically used in EPA-focused interventions and, depending on the target tissue and physiological demand, may partially satisfy DHA requirements. This nuanced understanding is critical for the development of evidence-based dietary recommendations and sustainable omega-3 supplementation strategies.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":" ","pages":"417-426"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Hypothesis for the Protective Rise in Cholesterol Sulfate Against Lipid Metabolic Disorders.","authors":"Xiaoyue Li, Chengcheng Wang, Yuming Wang, Tiantian Zhang","doi":"10.1002/lipd.70031","DOIUrl":"10.1002/lipd.70031","url":null,"abstract":"<p><p>As a cholesterol metabolite, cholesterol sulfate (CS) is widely distributed in the human body, and its role as a regulatory factor has been continuously explored from the 1980s to the present day. However, changes in CS in metabolic disorders have not been systematically investigated. Here, rodent models of insulin resistance, fatty liver, and atherosclerosis were established. The CS content, CS to cholesterol ratio, and CS to total bile acids (TBA) ratio in the serum and liver of these model mice were compared with those of normal mice. Results showed the CS content was increased in fatty liver and atherosclerosis models of mice; meanwhile, it might be influenced by genotype, such as CD36 deficiency. The changes in the CS to cholesterol ratio were related to the amount and distribution of cholesterol. Besides, there was competition between the catabolism of cholesterol to bile acids or CS, as evidenced by the opposite trend between the TBA to cholesterol ratio and the CS to TBA ratio. Moreover, for the first time, it has been discovered that CS is enriched in lipid droplets, which further substantiates the close association between CS and lipid metabolism. Building on studies that demonstrated the beneficial effects of CS supplementation in alleviating lipid metabolic disorders, we first proposed the hypothesis that an increase in CS content may be protective against lipid metabolic disorders. This study provided a new perspective on the role of CS as a regulatory factor in metabolic disorders.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":" ","pages":"309-317"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Lipid Biology-Associated Gene Expression in Granulosa Cells in Hyperandrogenic PCOS: A Possible Link Between Dyslipidemia and Hyperandrogenism.","authors":"Caglar Berkel","doi":"10.1002/lipd.70035","DOIUrl":"10.1002/lipd.70035","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a heterogeneous reproductive endocrine condition in women, with implications in fertility and long-term metabolic health. PCOS with hyperandrogen (HA-PCOS; hyperandrogenic PCOS) has been recently identified as one of the four subtypes of PCOS. Dyslipidemia is known to be associated with clinical hyperandrogenism in PCOS. Indeed, patients with HA-PCOS were found to have the highest incidence of dyslipidemia among patients with the other three subtypes of PCOS. In the present study, we identified genes involved in lipid-associated processes (namely, lipid biosynthetic process, lipid catabolic process, hyperlipidemia, hypolipidemia and lipid homeostasis) whose expression are changed in granulosa cells from HA-PCOS patients compared to those from non-PCOS women, in order to identify molecular factors contributing to the highest risk of dyslipidemia incidence observed in patients with hyperandrogenic PCOS. We found 27 lipid biology-associated genes (ACSM1, ACSM3, AGPAT4, AJUBA, ALDH1A2, CCDC3, LPL, P2RX1, PITPNM1, PRLR, PTGIS, SLC44A5, SPTSSB, ST8SIA5, IDH1, ITPKA, PPM1L, SPTLC2, ADRA2A, ASPG, IRS1, PLB1, IDH1, LCT, NUDT8, SMPDL3A and SYNE2) whose transcript levels are significantly downregulated or upregulated in granulosa cells of women with HA-PCOS compared to those in control women. The majority of these genes have not been previously studied in the context of PCOS, and are possible candidates for further research to better understand the contribution of high androgen levels to dyslipidemia in PCOS. Targeting of high androgen-induced dyslipidemia might be of high clinical importance in the treatment of women with HA-PCOS.</p>","PeriodicalId":18086,"journal":{"name":"Lipids","volume":"61 3","pages":"363-370"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}