The raw data files generated by the UPLC-MS/MS system were processed using TMBQ software (version 1.0, Metabo-Profile, Shanghai, China) to perform automated peak integration, calibration, and absolute quantitation for each targeted metabolite.
"],"repository":["MetaboLights"],"study_status":["Public"],"ptm_modification":[""],"instrument_platform":["Liquid Chromatography MS - alternating - reverse-phase"],"chromatography_protocol":["A series of gradient-diluted derivatized standard solutions were utilized as quality control samples prior to the LC-MS analysis to ensure instrument stability. The quantitation of all targeted metabolites was conducted using an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system (ACQUITY UPLC-Xevo TQ-S, Waters Corp., Milford, MA, USA), with analytical support from Metabo-Profile Biotechnology (Shanghai) Co., Ltd. For the HPLC separation, the system was equipped with an ACQUITY UPLC BEH C18 VanGuard precolumn (2.1 x 50 mm, 1.7 um) and an ACQUITY UPLC BEH C18 analytical column (2.1 x 100 mm, 1.7 um). The column temperature was maintained at 40 C, and the sample manager was set to 10 C. The mobile phases consisted of water with 0.1% formic acid (Solvent A) and a mixture of acetonitrile/isopropanol (70:30, Solvent B). The chromatographic separation was achieved using the following gradient elution profile at a constant flow rate of 0.40 mL/min: 0-1 min, 5% B; 1-11 min, 5-78% B; 11-13.5 min, 78-95% B; 13.5-14 min, 95-100% B; 14-16 min, 100% B; 16-16.1 min, 100-5% B; and 16.1-18 min, 5% B. The injection volume was 5.0 uL.
"],"publication":["Intermittent fasting mobilizes polyunsaturated fatty acid eicosapentaenoic acid inducing ferroptosis to suppress hepatocellular carcinoma progression."],"submitter_affiliation":["Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China"],"submitter_name":["Yanyu Jiang"],"organism_part":["liver"],"technology_type":["mass spectrometry assay"],"disease":[""],"extraction_protocol":["120 μL of methanol containing an internal standard was added to extract the metabolites. The mixture was homogenized for another 3 minutes and centrifuged at 18,000 × g for 20 minutes. The supernatant was then transferred to a 96-well plate. Subsequent derivatization procedures were performed on an Eppendorf epMotion Workstation (Eppendorf Inc., Hamburg, Germany). Briefly, 20 μL of freshly prepared derivative reagents was added to each well. The plate was sealed, and derivatization was carried out at 30 °C for 60 minutes. After derivatization, the samples were evaporated for 2 hours and reconstituted in 330 μL of ice-cold 50% methanol solution. The plate was incubated at −20 °C for 20 minutes, followed by centrifugation at 4,000 × g at 4 °C for 30 minutes. Finally, 135 μL of the supernatant was transferred to a new 96-well plate containing 10 μL of internal standards in each well. Serial dilutions of derivatized stock standards were loaded into the leftmost wells as quality control samples, and the plate was sealed for immediate LC-MS analysis.
"],"organism":["Mus musculus"],"full_dataset_link":["https://www.ebi.ac.uk/metabolights/MTBLS15484"],"author":["Lijun Jia. Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.. jialijun2002@aliyun.com.","Biying Xiao. Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.. xby3281@163.com.","Yanyu Jiang. Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 675946385@qq.com."],"data_transformation_protocol":["The raw data files generated by the UPLC-MS/MS system were processed using TMBQ software (version 1.0, Metabo-Profile, Shanghai, China) to perform automated peak integration, calibration, and absolute quantitation for each targeted metabolite. Following initial data validation, comprehensive statistical analyses and data visualization were executed utilizing website (https://www.metaboanalyst.ca/home.xhtml) and Graphpad Prism11. The analytical workflow included Principal Component Analysis (PCA) for unsupervised pattern recognition, Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) to identify discriminative features between groups, univariate analyses (including Student's t-tests), and pathway enrichment analysis. Metabolites meeting the predefined thresholds of a Variable Importance in Projection (VIP) score >= 1 and an adjusted p-value < 0.05 were classified as significantly differentially expressed.
"],"study_factor":["Treatment"],"submitter_email":["675946385@qq.com"],"sample_collection_protocol":["Targeted metabolomic analysis was performed on liver tissue samples collected from a total of 10 MAFLD-associated HCC mice, from the control group (n = 5) and the fasting group (n = 5). Each harvested tissue sample (10 mg) was stored in an Eppendorf Safe-Lock microcentrifuge tube, mixed with 10 pre-chilled zirconium oxide beads and 20 μL of deionized water, and homogenized for 3 minutes.
"],"omics_type":["Metabolomics"],"study_design":["Metabolomics","Mus musculus","Fasting","Waters Xevo TQ-S","targeted analysis","liver","mafld-hcc","EPA","Waters ACQUITY UPLC system","experimental blank"],"curator_keywords":["Metabolomics","Mus musculus","Fasting","Waters Xevo TQ-S","targeted analysis","liver","mafld-hcc","EPA","Waters ACQUITY UPLC system","experimental blank"],"mass_spectrometry_protocol":["The Waters Xevo TQ-S mass spectrometer was operated with the following optimized parameters: capillary voltages of 1.5 kV (ESI+) and 2.0 kV (ESI-), source temperature of 150 C, desolvation temperature of 550 C, and a desolvation gas flow of 1000 L/h.
"],"metabolite_name":["Glucaric acid","12-KetoLCA","Butyric acid","Heptanoic acid","beta-Alanine","Ketoleucine","Myristoleic acid","Methionine","4-Hydroxyhippuric acid","Oxoglutaric acid","alpha-Ketoisovaleric acid","N-Acetyl-D-glucosamine","Citrulline","2-Methylbutyroylcarnitine","bHDCA","DHA","4-Hydroxyproline","Undecanoic acid","Ricinoleic acid","Lactulose","Pyruvic acid","Butyrylcarnitine","Glycine","3,4-Dihydroxymandelic acid","9-Pentadecenoic acid","N-Acetylglutamine","Palmitelaidic acid","Arginine","Oleic acid","Glutaric acid","Pentadecanoic acid","10Z-Nonadecenoic acid","CA","CDCA","Phenylalanine","Methylcysteine","5-Hydroxylysine","TCDCA","Indole-3-propionic acid","1H-Indole-3-acetamide","HDCA","Hexanylcarnitine","N-Acetylneuraminic acid","Indolelactic acid","N-Acetyl-L-methionine","Glyceraldehyde","Creatine","Aminocaproic acid","Shikimic acid","2,3-Diaminopropionic acid","5-Aminolevulinic acid","Ribulose","Acetylglycine","Glycyleucine","N-Acetyalanine","Glyceric acid","Tetradecanoylcarnitine","Tyrosine","Phthalic acid","Oleylcarnitine","N-Acetytyrosine","Aminoadipic acid","Xylose","Myristic acid","Rhamnose","Succinic acid","GABA","Hydroxypropionic acid","Phenyllactic acid","Adipic acid","Acetic acid","Ornithine","Gluconolactone","Adrenic acid","Homoserine","gamma-Linolenic acid","Decanoic acid","Malonic acid","Hippuric acid","alpha-Linolenic acid","Isovalerylcarnitine","Serine","Proline","Isocitric acid","Tridecanoic acid","Homovanillic acid","Glutarylcarnitine","Aspartic acid","2-Hydroxybutyric acid","Isoleucine","GCA","2-Methy-4-pentenoic acid","Glutaconic acid","Homocitrulline","5-Hydroxy-tryptophan","TDCA","Dodecanoylcarnitine","Threonic acid","Oxoadipic acid","Fructose","Linoleic acid","Aconitic acid","Isobutyric acid","TLCA","Fumaric acid","Palmitoleic acid","Acetylcarnitine","EPA","Citraconic acid","Stearylcarnitine","3-Hydroxybutyric acid","Dimethylglycine","3-Hydroxyphenylacetic acid","Glutamine","Benzoic acid","Phenylpyruvic acid","bUDCA","Phenylacetic acid","Adipoylcarnitine","Caproic acid","5Z-Dodecenoic acid","Methylsuccinic acid","UDCA","Glucose","Arachidonic acid","Protocatechuic acid","Glycylproline","Histidine","Melibiose","Anserine","N-Acetyaspartic acid","Malonylcarnitine","Threonine","Propionic acid","Nonanoic acid","p-Hydroxyphenylacetic acid","Maltotriose","Propionylcarnitine","Valeric acid","Sebacic acid","DPA","2-Methylpentanoic acid","Lysine","Methylmalonylcarnitine","Glutamic acid","Suberic acid","TUDCA","aMCA","isoDCA","Galactonic acid","10Z-Heptadecenoic acid","GCDCA","9E-tetradecenoic acid","Picolinic acid","Xylulose","N-Acetylserine","Pyroglutamic acid","Kynurenine","3-Pyridylacetic acid","Hydroxyphenyllactic acid","Alanine","Petroselinic acid","Linoelaidic acid","Tryptophan","Pimelic acid","Citric acid","Fructose 6-phosphate","UCA","Valine","Asparagine","3-Methyl-2-oxopentanoic acid","Erythronic acid","Valerylcarnitine","Isocaproic acid","Itaconic acid","Methylmalonic acid","Glucose 6-phosphate","N-Phenylacetylphenylalanine","Maleic acid","Malic acid","ortho-Hydroxyphenylacetic acid","DCA","wMCA","AMP","Mandelic acid","2-Hydroxy-3-methylbutyric acid","Palmitoylcarnitine","Indole-3-pyruvic acid","Carnitine","TCA","gamma-Glutamylalanine","SAH","Ribose 5-phosphate","3,4-Dihydroxyhydrocinnamic acid","1-Methylhistidine","Leucine","Citramalic acid","Dihomo-gamma-linolenic acid","DPAn-6","Azelaic acid","Imidazolepropionic acid","bMCA","GUDCA","Tartaric acid","2-Hydroxyglutaric acid","Sarcosine","Lactic acid","alpha-Aminobutyric acid"],"additional_accession":[]},"is_claimable":false,"name":"Intermittent fasting mobilizes polyunsaturated fatty acid eicosapentaenoic acid inducing ferroptosis to suppress hepatocellular carcinoma progression","description":"Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a leading cause of hepatocellular carcinoma (HCC), prompting ongoing efforts to understand its mechanisms and develop targeted therapies. Although dietary interventions such as fasting influence tumor growth, the underlying molecular pathways remain unclear. Here we show that intermittent fasting elevates eicosapentaenoic acid mobilization, which subsequently suppresses hepatocellular carcinoma progression by inducing ferroptosis. Mechanistically, this fatty acid acts as a signaling mediator by binding G protein-coupled receptor 120 (GPR120). This interaction activates the retinoid X receptor alpha (RXRα) and peroxisome proliferator-activated receptor alpha heterodimer (PPARα), upregulating cytochrome P450 oxidoreductase (POR) transcription and executing ferroptosis. We validate this pathway using orthotopic and genetic mouse models along with patient-derived organoids. With clinical data confirming that reduced cytochrome P450 oxidoreductase expression correlates with poor patient prognosis, these findings suggest eicosapentaenoic acid (EPA) supplementation as a potential fasting-mimetic strategy for disease management.","dates":{"publication":"2026-08-28","submission":"2026-08-28"},"accession":"MTBLS15484","cross_references":{"HMDB":["HMDB0002006","HMDB0000450","HMDB0000182","HMDB0000177","HMDB0000517","HMDB0000214","HMDB0000641","HMDB0000148","HMDB0000194","HMDB0000271","HMDB0000056","HMDB0000161","HMDB0000092","HMDB0000112","HMDB0000187","HMDB0000167","HMDB0000719","HMDB0000064","HMDB0000943","HMDB0000700","HMDB0001901","HMDB0001538","HMDB0000721","HMDB0000679","HMDB0000045","HMDB0029739","HMDB0000190","HMDB0002108","HMDB0000158","HMDB0000423","HMDB0000472","HMDB0000168","HMDB0001856","HMDB0000159","HMDB0000755","HMDB0000759","HMDB0013678","HMDB0000684","HMDB0000191","HMDB0000510","HMDB0000663","HMDB0000407","HMDB0002243","HMDB0000669","HMDB0000714","HMDB0000766","HMDB0000156","HMDB0000812","HMDB0000866","HMDB0031158","HMDB0001870","HMDB0000209","HMDB0000134","HMDB0000661","HMDB0000072","HMDB0002302","HMDB0002372","HMDB0000784","HMDB0000792","HMDB0000019","HMDB0000695","HMDB0000491","HMDB0000205","HMDB0000202","HMDB0000606","HMDB0000123","HMDB0000904","HMDB0000565","HMDB0000150","HMDB0000452","HMDB0000139","HMDB0000162","HMDB0000532","HMDB0000613","HMDB0002931","HMDB0003070","HMDB0006029","HMDB0000230","HMDB0000048","HMDB0000042","HMDB0000883","HMDB0000267","HMDB0001149","HMDB0000122","HMDB0001866","HMDB0000740","HMDB0001262","HMDB0000357","HMDB0000696","HMDB0000008","HMDB0000620","HMDB0000172","HMDB0000687","HMDB0000098","HMDB0000621","HMDB0001644","HMDB0000849","HMDB0000660","HMDB0000215","HMDB0000237","HMDB0001051","HMDB0000118","HMDB0000020","HMDB0000929","HMDB0000039","HMDB0001873","HMDB0000703","HMDB0000691","HMDB0000956","HMDB0000892","HMDB0000779","HMDB0000176","HMDB0002092","HMDB0000634","HMDB0001844","HMDB0000448","HMDB0002107","HMDB0000857","HMDB0031580","HMDB0000689","HMDB0000535","HMDB0000893","HMDB0000874","HMDB0000036","HMDB0000094","HMDB0000193","HMDB0000666","HMDB0000243","HMDB0000896","HMDB0000951","HMDB0000364","HMDB0000506","HMDB0000208","HMDB0000708","HMDB0000722","HMDB0000664","HMDB0000946","HMDB0000733","HMDB0000619","HMDB0000225","HMDB0000138","HMDB0000847","HMDB0000511","HMDB0000518","HMDB0000637","HMDB0000947","HMDB0000529","HMDB0000910","HMDB0002000","HMDB0062248","HMDB0034297","HMDB0000626","HMDB0000806","HMDB0029765","HMDB0000826","HMDB0003229","HMDB0012328","HMDB0060038","HMDB0001388","HMDB0003073","HMDB0000673","HMDB0006270","HMDB0001999","HMDB0001043","HMDB0002925","HMDB0002183","HMDB0006528","HMDB0001976","HMDB0002226","HMDB0000254","HMDB0000426","HMDB0000207","HMDB0002080","HMDB0013622","HMDB0000440","HMDB0000062","HMDB0000201","HMDB0000824","HMDB0002095","HMDB0002013","HMDB0000378","HMDB0013128","HMDB0000688","HMDB0013130","HMDB0000705","HMDB0061677","HMDB0002250","HMDB0005066","HMDB0000222","HMDB0005065","HMDB0000848","HMDB0000124","HMDB0001548","HMDB0001401","HMDB0002536","HMDB0013133","HMDB0000939","HMDB0000917","HMDB0000415","HMDB0000686","HMDB0000328","HMDB0011745","HMDB0000671","HMDB0060484","HMDB0000001","HMDB0000725","HMDB0006248","HMDB0002271"]}}