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

Integrated proteomic and metabolomic analysis reveals lipid metabolic dysregulation and ferroptosis as potential drivers of placental dysfunction in intrahepatic cholestasis of pregnancy 综合蛋白质组学和代谢组学分析显示，脂质代谢失调和铁下沉是妊娠肝内胆汁淤积中胎盘功能障碍的潜在驱动因素

IF 3.3 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-10-03 DOI: 10.1016/j.bbalip.2025.159692

Ruirui Dong , Gaoying Wang , Yingxian Shi , Jianyi Gao , Wen Hu , Ting Zhang

{"title":"Integrated proteomic and metabolomic analysis reveals lipid metabolic dysregulation and ferroptosis as potential drivers of placental dysfunction in intrahepatic cholestasis of pregnancy","authors":"Ruirui Dong , Gaoying Wang , Yingxian Shi , Jianyi Gao , Wen Hu , Ting Zhang","doi":"10.1016/j.bbalip.2025.159692","DOIUrl":"10.1016/j.bbalip.2025.159692","url":null,"abstract":"<div><div>Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse fetal outcomes, while current biomarkers such as total bile acid remain suboptimal. This study aimed to identify novel biomarkers and clarify metabolic pathways underlying ICP through integrated metabolomic and proteomic analyses. Placental profiles were obtained from ICP model rats and healthy controls, with differential metabolites and proteins validated in human placental and serum samples. Multiomics integration revealed prominent dysregulation of lipid metabolism, particularly fatty acid degradation and biosynthesis, highlighting lipids as central players in ICP. Palmitic acid and acyl-CoA synthetase long chain family member 1 (ACSL1) were central to these pathways, markedly elevated in ICP, and showed high diagnostic value (area under the curve 0.794 and 0.825), with combined detection reaching 0.894. Both markers also stratified patients by disease severity, suggesting their potential use for disease monitoring and risk classification. Moreover, ferroptosis was implicated in ICP pathophysiology, supported by validations in both patient placental tissues and taurocholic acid (TCA)-treated trophoblast cells, showing reduced glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) together with increased six-transmembrane epithelial antigen of prostate 3 (STEAP3), transferrin receptor protein 1 (CD71), and acyl-CoA synthetase long-chain family member 4 (ACSL4). In summary, palmitic acid and ACSL1 represent promising biomarkers for ICP diagnosis and classification, while ferroptosis contributes to ICP-related placental dysfunction. These findings provide comprehensive evidence linking altered lipid metabolism and ferroptosis to ICP, offering new insights for clinical diagnosis and potential therapeutic strategies.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 1","pages":"Article 159692"},"PeriodicalIF":3.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Distinct lipidomic profiles in breast cancer cell lines relate to proliferation and EMT phenotypes. 乳腺癌细胞系中不同的脂质组学特征与增殖和EMT表型有关。

IF 3.3 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-10-01 Epub Date: 2025-08-05 DOI: 10.1016/j.bbalip.2025.159679

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

{"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}

引用次数: 0

The B-lymphoblastoid model in Barth syndrome 巴斯综合征的b淋巴母细胞样细胞模型。

IF 3.3 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-09-23 DOI: 10.1016/j.bbalip.2025.159691

John Z. Chan , Michelle V. Tomczewski , Antonia N. Berdeklis , Robin E. Duncan

{"title":"The B-lymphoblastoid model in Barth syndrome","authors":"John Z. Chan , Michelle V. Tomczewski , Antonia N. Berdeklis , Robin E. Duncan","doi":"10.1016/j.bbalip.2025.159691","DOIUrl":"10.1016/j.bbalip.2025.159691","url":null,"abstract":"<div><div>Barth Syndrome (BTHS) is an ultra-rare, X-linked mitochondrial disorder caused by a variety of different mutations in the cardiolipin remodeling gene <em>TAFAZZIN</em> that results in cardiac and skeletal myopathy, as well as immunological deficits. Epstein-Barr virus-mediated transformation of B-lymphocytes has been used to generate B-lymphoblastoid cells that retain many of the characteristics of the initial cell line, but can be propagated extensively in culture to generate biological materials enabling study of the basic, natural function of this enzyme in cells, as well as disease-relevant effects and interventions. Notably, these model lines from individual donors are of particular value for understanding a disease with variable penetrance such as BTHS, where variation in genetic background can alter symptom severity considerably, even among closely-related individuals with the same mutation. Here, we review the generation, benefits, and limitations of the B-lymphoblastoid cell model in BTHS research, and provide an overview of recent advances in understanding the role of TAFAZZIN in mitochondrial biology from this model. Implications of these findings for understanding the pathology of BTHS, and determining future directions, are also provided, along with a review of recent advances in our understanding of the mechanism of TAFAZZIN function in cardiolipin degradation, remodeling and stability.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 8","pages":"Article 159691"},"PeriodicalIF":3.3,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ApoB: The intracellular protein detection dilemma in lipoprotein biology 载脂蛋白ob：脂蛋白生物学中细胞内蛋白检测的困境。

IF 3.3 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-09-13 DOI: 10.1016/j.bbalip.2025.159690

Ankia Visser , Floris A. Feiner , Willemien Heerema-van Zwol , Marieke Smit , Nicolette C.A. Huijkman , Niels J. Kloosterhuis , Henry N. Ginsberg , Bart van de Sluis , Jan Albert Kuivenhoven

引用次数: 0

Pulmonary surfactant protein SP-C regulates lipid vesicle uptake by alveolar type II cells and macrophages: Role of lipids, palmitoylation, and environment 肺表面活性蛋白SP-C调节肺泡II型细胞和巨噬细胞对脂质囊泡的摄取：脂质、棕榈酰化和环境的作用

IF 3.3 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-09-08 DOI: 10.1016/j.bbalip.2025.159688

Mishelle Morán-Lalangui , Marta Villoslada-González , Carmen Hevia-Lorenzo , Jesús Pérez-Gil , Begoña García-Álvarez

{"title":"Pulmonary surfactant protein SP-C regulates lipid vesicle uptake by alveolar type II cells and macrophages: Role of lipids, palmitoylation, and environment","authors":"Mishelle Morán-Lalangui , Marta Villoslada-González , Carmen Hevia-Lorenzo , Jesús Pérez-Gil , Begoña García-Álvarez","doi":"10.1016/j.bbalip.2025.159688","DOIUrl":"10.1016/j.bbalip.2025.159688","url":null,"abstract":"<div><div>Pulmonary surfactant protein C (SP-C) may play a key role in alveolar homeostasis by modulating vesicle uptake in alveolar cells. This study explores how SP-C regulates internalization of model unilamellar lipid vesicles by type II alveolar epithelial cells (AECII) and alveolar macrophages (AMϕ), focusing on the effect of lipid composition, palmitoylation state, and interactions with external stimuli like lipopolysaccharides (LPS) or the other hydrophobic surfactant protein SP-B. Using fluorescence-based techniques, we demonstrated that SP-C enhances vesicle uptake in a lipid-dependent manner. While AECII internalize vesicles regardless of lipid composition, AMϕ show a preference for vesicles with specific lipid profiles. The palmitoylation of SP-C is essential for efficient vesicle uptake, highlighting the importance of membrane-protein interactions in this process. Furthermore, SP-C colocalizes with acidic organelles within both cell types, suggesting its involvement in intracellular trafficking and surfactant homeostasis. Notably, SP-C facilitates LPS uptake by AMϕ, potentially contributing to immune modulation in the alveolar spaces. The contribution of SP-C to metabolism and pulmonary immunity has important implications in lung diseases involving surfactant dysfunction or immune dysregulation.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 8","pages":"Article 159688"},"PeriodicalIF":3.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hypertriglyceridemia impairs HDL functionality, promotes macrophage metabolic activation and exacerbates antigen-induced rheumatoid arthritis in mice which can be reversed by fenofibrate treatment 高甘油三酯血症损害HDL功能，促进巨噬细胞代谢激活，加剧抗原诱导的类风湿性关节炎，非诺贝特治疗可逆转。

IF 3.3 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-09-08 DOI: 10.1016/j.bbalip.2025.159686

Isidoros Axiotis , Asimina Kakale , Despina Lazaridou , Anastasia-Georgia Dedemadi , Angeliki Chroni , Marius Multescu , Anca Violeta Gafencu , Maria Tzardi , Dimitris Kardassis

{"title":"Hypertriglyceridemia impairs HDL functionality, promotes macrophage metabolic activation and exacerbates antigen-induced rheumatoid arthritis in mice which can be reversed by fenofibrate treatment","authors":"Isidoros Axiotis , Asimina Kakale , Despina Lazaridou , Anastasia-Georgia Dedemadi , Angeliki Chroni , Marius Multescu , Anca Violeta Gafencu , Maria Tzardi , Dimitris Kardassis","doi":"10.1016/j.bbalip.2025.159686","DOIUrl":"10.1016/j.bbalip.2025.159686","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is associated with increased cardiovascular disease (CVD) risk, partly attributed to altered lipid metabolism. Apolipoprotein C-III (ApoC-III), a key regulator of triglyceride-rich lipoproteins in the plasma, has been implicated in both dyslipidemia and inflammation. In this study, we investigated the role of hypertriglyceridemia in RA using a transgenic mouse model overexpressing the human ApoC-III gene (ApoC-III Tg). Using a protocol of antigen-induced arthritis (AIA), we show that ApoC-III Tg mice exhibited significantly greater joint swelling, inflammatory infiltration and cartilage destruction compared to non-transgenic controls. These changes were accompanied by altered lipoprotein distribution in serum and High Density Lipoprotein (HDL) dysfunction including reduced antioxidant function. Furthermore, HDL isolated from arthritic ApoC-III Tg mice had pro-inflammatory properties on macrophages as demonstrated by the increased expression of iNOS and IL1β as well as increased mitochondrial respiration. Treatment of arthritic ApoC-III Tg mice with fenofibrate, a triglyceride-lowering drug, reduced triglyceride levels and increased ApoA-I content in HDL fractions. Importantly, fenofibrate significantly ameliorated arthritis severity, restored HDL antioxidant function and reduced macrophage activation. These findings highlight a mechanistic link between dyslipidemia, HDL dysfunction, and inflammatory exacerbation in RA and suggest that targeting ApoC-III-associated pathways may offer therapeutic benefit in patients with coexisting metabolic and inflammatory disorders.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 8","pages":"Article 159686"},"PeriodicalIF":3.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 3.3 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-09-07 DOI: 10.1016/j.bbalip.2025.159687

Philipp W. Weiß , Philip P. Kaltenborn , Christiane Frahm , Ulrike Schulze-Späte , Estelle Heyne , Marten Szibor , Sandor Nietzsche , Ralf A. Claus , Markus H. Gräler

{"title":"Age-related changes in cardiolipin profile and functional consequences of altered fatty acid supply","authors":"Philipp W. Weiß , Philip P. Kaltenborn , Christiane Frahm , Ulrike Schulze-Späte , Estelle Heyne , Marten Szibor , Sandor Nietzsche , Ralf A. Claus , Markus H. Gräler","doi":"10.1016/j.bbalip.2025.159687","DOIUrl":"10.1016/j.bbalip.2025.159687","url":null,"abstract":"<div><div>Cardiolipins (CLs) are primarily expressed in the inner mitochondrial membrane where they play essential roles in membrane architecture and mitochondrial functions. CLs have a unique structure characterized by four acyl chains with different stoichiometries such as chain length and degree of saturation. CL composition changes with disease and age, but it is largely unknown how dynamic changes affect mitochondrial function. Here, we compared CL profiles in different mouse tissues across different age groups using liquid chromatography and triple quadrupole mass spectrometry. A key finding was that CLs in the brain differ significantly from those in peripheral organs, with a tendency towards longer-chain variants. We hypothesized that these differences may be influenced by the availability of fatty acids (FA), which in the brain could be affected by the blood-brain barrier. In support of this notion, we found that FA concentrations varied in the different compartments. In addition, we found that CL profiles changed during aging. In cultivated macrophages supplemented with different FAs, we tested how altered CL profiles may affect both, mitochondrial morphology and function such as cristae density, and mitochondrial membrane potential and respiration, respectively. Finally, we validated our <em>in vitro</em> results <em>in vivo</em> by altering the CL profile in mice by using palmitic acid and oleic acid enriched diets. Our study highlights a dynamic adaptation of CL profiles in response to FA availability and aging and emphasizes its functional importance for mitochondrial function. Furthermore, FA supplementation may be a promising therapeutic strategy to address disease- and age-related mitochondrial malfunctions.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 8","pages":"Article 159687"},"PeriodicalIF":3.3,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular basis for regulation of the class I phosphoinositide 3-kinases (PI3Ks), and their targeting in human disease I类磷酸肌肽3激酶（pi3k）调控的分子基础及其在人类疾病中的靶向作用。

IF 3.3 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-09-07 DOI: 10.1016/j.bbalip.2025.159689

Alexandria L. Shaw , Isobel Barlow-Busch , John E. Burke

{"title":"Molecular basis for regulation of the class I phosphoinositide 3-kinases (PI3Ks), and their targeting in human disease","authors":"Alexandria L. Shaw , Isobel Barlow-Busch , John E. Burke","doi":"10.1016/j.bbalip.2025.159689","DOIUrl":"10.1016/j.bbalip.2025.159689","url":null,"abstract":"<div><div>The class I phosphoinositide 3-kinase pathway (PI3K) is a master regulator of cellular growth, and plays essential roles in controlling immune cell function, metabolism, chemotaxis and proliferation. Activation of class I PI3Ks generates the signalling lipid PIP<sub>3</sub> that activates multiple pro-growth signalling pathways. Class I PI3Ks can be activated by multiple plasma membrane stimuli, including G-protein coupled receptors, Ras superfamily GTPases, and receptor tyrosine kinases. The dysregulation of class I PI3Ks is critical in the progression of many human diseases, including cancers, immunodeficiencies, and developmental disorders. Highlighting this is frequent oncogenic mutations (2nd most frequently mutated gene in all human cancers) in <em>PIK3CA</em> encoding the p110α catalytic subunit of class IA PI3K. The class I PI3Ks are obligate heterodimers composed of a catalytic and regulatory subunit, split into two subclasses, class IA and class IB. Recent elucidation of the structures of class I PI3Ks bound to activating stimuli, with activating disease-linked mutations and bound to allosteric conformational selective inhibitors/activators, has revealed extensive insight into the molecular basis of class I PI3K regulation. This review will summarize our current molecular knowledge of class I PI3K regulation, as well as how this information is being used to generate both small molecules and biologics that can either inhibit or activate kinase activity as potential therapeutic agents and biochemical tools.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 8","pages":"Article 159689"},"PeriodicalIF":3.3,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combination of hydroxycitric acid and capsaicin regulates IRS-1/AMPK-mTOR-SREBP-1c Axis/NLRP3-NF-κB/Nrf-2-ARE signaling pathways to ameliorate the two-hit process in high-fat diet-induced hepatic steatosis 羟基柠檬酸和辣椒素联合调控IRS-1/AMPK-mTOR-SREBP-1c Axis/NLRP3-NF-κB/Nrf-2-ARE信号通路，改善高脂饮食诱导的肝脂肪变性的双击过程

IF 3.3 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-08-23 DOI: 10.1016/j.bbalip.2025.159682

V V Sathibabu Uddandrao , Deepthi Krishna , Mallenahalli Neelakantappa Vasantha , G. Jayashree , Anitha Roy , V.R. Ravikkumar , S. Sengottuvelu , P. Chandrasekaran , C. Kathirvelan , Brahma Naidu Parim , Kaushik Das , Umesh Kumar

{"title":"Combination of hydroxycitric acid and capsaicin regulates IRS-1/AMPK-mTOR-SREBP-1c Axis/NLRP3-NF-κB/Nrf-2-ARE signaling pathways to ameliorate the two-hit process in high-fat diet-induced hepatic steatosis","authors":"V V Sathibabu Uddandrao , Deepthi Krishna , Mallenahalli Neelakantappa Vasantha , G. Jayashree , Anitha Roy , V.R. Ravikkumar , S. Sengottuvelu , P. Chandrasekaran , C. Kathirvelan , Brahma Naidu Parim , Kaushik Das , Umesh Kumar","doi":"10.1016/j.bbalip.2025.159682","DOIUrl":"10.1016/j.bbalip.2025.159682","url":null,"abstract":"<div><div>Metabolic (Dysfunction) Associated Steatotic Liver Disease (MASLD) is a complex metabolic condition, the progression of which toward steatohepatitis can be explained by the ‘two-hit’ hypothesis: the first hit involves lipid accumulation, and the second hit involves inflammation and oxidative stress. In this study, we aimed to evaluate the protective effects of a combination of hydroxycitric acid and capsaicin (CHC) against high-fat diet (HFD)-induced MASLD in rats, specifically by targeting the mechanisms associated with both hits. To establish the experimental model, rats were fed a HFD for 16 weeks, followed by treatment with CHC for 6 weeks starting on day one of the 16th week of HFD feeding. CHC treatment effectively mitigated the first hit by improving insulin sensitivity via IRS-1 upregulation and activating AMPK signaling, which in turn inhibited mTOR activity and suppressed key lipogenic markers including SREBP-1c, FAS, ACC, and PPAR-γ. Simultaneously, CHC countered the second hit by enhancing antioxidant defense through Nrf-2 and HO-1 upregulation, while attenuating hepatic inflammation via downregulation of NF-κB, TNF-α, IL-6, and NLRP3 at both mRNA and protein levels. In conclusion, CHC can effectively protect against MASLD in HFD-fed rats by defending against the “first and second hit” by mediating the IRS-1/AMPK-mTOR-SREBP-1c axis/NLRP3-NF-κB/Nrf-2-ARE signaling pathways.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 8","pages":"Article 159682"},"PeriodicalIF":3.3,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sterol analysis of MARCHF6-deficient cells reveals a new pinch point in the cholesterol biosynthesis pathway 对marchf6缺陷细胞的甾醇分析揭示了胆固醇生物合成途径中的一个新点

IF 3.3 2区生物学

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-08-22 DOI: 10.1016/j.bbalip.2025.159684

Nicole M. Fenton , Laura J. Sharpe , Andrew M. Jenner , Andrew J. Brown

引用次数: 0