{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T16:40:38Z","timestamp":1789836038188,"version":"4.0.1"},"reference-count":206,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Primary liver cancer (PLC), commonly classified as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), is a highly aggressive malignancy with a dismal prognosis. Recent research has highlighted the crucial role of dysregulation of fatty acid metabolism in HCC progression and therapeutic resistance. Here, with a focus primarily on HCC, we review how alterations in the processes involving fatty acids dynamically contribute to the survival, proliferation, and development of the drug resistance of PLC cells. In particular, increased expression of fatty acid transporters, reprogramming of de novo lipogenesis, and altered fatty acid oxidation trigger the upregulation of oncogenic signaling pathways and adaptation to nutrient-deprived conditions inducing the rapid proliferation of PLC cells. Furthermore, fatty acid metabolism influences immune cell function and angiogenesis, thereby shaping the tumor microenvironment and promoting the progression of PLC. This review explores the complex relationship between fatty acid metabolism and the progression of PLC. It discusses future directions regarding the most promising druggable targets and their current status in clinical trials. Furthermore, it examines the advancement of innovative therapeutic strategies and highlights the significant challenges in targeting fatty acid metabolism. Finally, it discusses how precision therapies focused on fatty acid metabolism can be effectively integrated with current treatments.<\/jats:p>","DOI":"10.3390\/biom16020329","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T13:08:23Z","timestamp":1771592903000},"page":"329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting Fatty Acids in Liver Cancer: Molecular Insights and Drug Approaches"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6408-3613","authenticated-orcid":false,"given":"Antonio","family":"Cigliano","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Saint Camillus International University of Health Sciences, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dora","family":"Pischedda","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery, and Pharmacy, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Pandino","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5379-9387","authenticated-orcid":false,"given":"Grazia","family":"Galleri","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego F.","family":"Calvisi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery, and Pharmacy, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ejca.2021.11.023","article-title":"Global, regional and national burden of primary liver cancer by subtype","volume":"161","author":"Rumgay","year":"2022","journal-title":"Eur. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","article-title":"Cholangiocarcinoma 2020: The next horizon in mechanisms and management","volume":"17","author":"Banales","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1053\/j.gastro.2017.06.012","article-title":"Risk of hepatocellular cancer in hcv patients treated with direct-acting antiviral agents","volume":"153","author":"Kanwal","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.jhep.2017.09.012","article-title":"Association between non-alcoholic fatty liver disease and cancer incidence rate","volume":"68","author":"Kim","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/hep.29466","article-title":"Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease","volume":"67","author":"Estes","year":"2018","journal-title":"Hepatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/j.2040-4603.2014.tb00548.x","article-title":"Energy metabolism in the liver","volume":"4","author":"Rui","year":"2014","journal-title":"Compr. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/s41575-019-0217-8","article-title":"Metabolic rearrangements in primary liver cancers: Cause and consequences","volume":"16","author":"Satriano","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1053\/j.gastro.2010.12.006","article-title":"Increased lipogenesis, induced by AKT-mTORC1-RPS6 signaling, promotes development of human hepatocellular carcinoma","volume":"140","author":"Calvisi","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1002\/hep.28508","article-title":"Differential requirement for de novo lipogenesis in cholangiocarcinoma and hepatocellular carcinoma of mice and humans","volume":"63","author":"Li","year":"2016","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1158\/0008-5472.CAN-23-0966","article-title":"FASN inhibition decreases MHC-I degradation and synergizes with PD-L1 checkpoint blockade in hepatocellular carcinoma","volume":"84","author":"Huang","year":"2024","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1055\/s-0041-1731709","article-title":"Role of lipogenesis rewiring in hepatocellular carcinoma","volume":"42","author":"Zhou","year":"2022","journal-title":"Semin. Liver Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e20201606","DOI":"10.1084\/jem.20201606","article-title":"Lipid metabolism and cancer","volume":"218","author":"Bian","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.cmet.2013.05.017","article-title":"Cellular fatty acid metabolism and cancer","volume":"18","author":"Currie","year":"2013","journal-title":"Cell Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrc3483","article-title":"Cancer metabolism: Fatty acid oxidation in the limelight","volume":"13","author":"Carracedo","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/S1262-3636(07)70061-7","article-title":"Contribution of hepatic de novo lipogenesis and reesterification of plasma non esterified fatty acids to plasma triglyceride synthesis during non-alcoholic fatty liver disease","volume":"29","author":"Diraison","year":"2003","journal-title":"Diabetes Metab."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Shi, Q., Chen, J., Zou, X., and Tang, X. (2022). Intracellular Cholesterol Synthesis and Transport. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.819281"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nrm2330","article-title":"Membrane lipids: Where they are and how they behave","volume":"9","author":"Voelker","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/nrm2335","article-title":"Lipid signalling in disease","volume":"9","author":"Wymann","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.metabol.2014.04.003","article-title":"De novo lipogenesis in health and disease","volume":"63","author":"Ameer","year":"2014","journal-title":"Metabolism"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41416-019-0650-z","article-title":"Reprogramming of fatty acid metabolism in cancer","volume":"122","author":"Koundouros","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1007\/s11745-001-0809-2","article-title":"A new concept of cellular uptake and intracellular trafficking of long-chain fatty acids","volume":"36","author":"Stremmel","year":"2001","journal-title":"Lipids"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/S1388-1981(99)00137-7","article-title":"Membrane proteins implicated in long-chain fatty acid uptake by mammalian cells: CD36, FATP and FABPm","volume":"1441","author":"Abumrad","year":"1999","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_25","first-page":"139","article-title":"Role of CD36 in membrane transport of long-chain fatty acids","volume":"5","author":"Ibrahimi","year":"2002","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4893","DOI":"10.7150\/thno.36037","article-title":"CD36 tango in cancer: Signaling pathways and functions","volume":"9","author":"Wang","year":"2019","journal-title":"Theranostics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"14752","DOI":"10.1038\/srep14752","article-title":"Elevated free fatty acid uptake via CD36 promotes epithelial-mesenchymal transition in hepatocellular carcinoma","volume":"5","author":"Nath","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nature20791","article-title":"Targeting metastasis-initiating cells through the fatty acid receptor CD36","volume":"541","author":"Pascual","year":"2017","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","article-title":"Immunity, Inflammation, and Cancer","volume":"140","author":"Grivennikov","year":"2010","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3391","DOI":"10.1038\/s41467-019-11274-x","article-title":"ER-residential Nogo-B accelerates NAFLD-associated HCC mediated by metabolic reprogramming of oxLDL lipophagy","volume":"10","author":"Tian","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"113947","DOI":"10.1016\/j.yexcr.2024.113947","article-title":"Cancer-associated fibroblasts contributed to hepatocellular carcinoma recurrence and metastasis via CD36-mediated fatty-acid metabolic reprogramming","volume":"435","author":"Wang","year":"2024","journal-title":"Exp. Cell Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.freeradbiomed.2023.03.013","article-title":"SLC27A4-mediated selective uptake of mono-unsaturated fatty acids promotes ferroptosis defense in hepatocellular carcinoma","volume":"201","author":"Li","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1002\/hep.32344","article-title":"Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids","volume":"76","author":"Biancaniello","year":"2022","journal-title":"Hepatology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"14107","DOI":"10.1038\/s41598-019-50531-3","article-title":"Unraveling FATP1, regulated by ER-\u03b2, as a targeted breast cancer innovative therapy","volume":"9","author":"Mendes","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"31937","DOI":"10.1038\/s41598-025-17143-6","article-title":"Long chain fatty acid transport via SLC27A1 enhances DAG-3-P synthesis and accelerates colorectal cancer metastasis","volume":"15","author":"Tong","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1158\/1541-7786.MCR-23-0389","article-title":"FATP5 Is Indispensable for the Growth of Intrahepatic Cholangiocarcinoma","volume":"22","author":"Wang","year":"2024","journal-title":"Mol. Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.cmet.2019.11.010","article-title":"Greasing the Wheels of the Cancer Machine: The Role of Lipid Metabolism in Cancer","volume":"31","author":"Snaebjornsson","year":"2020","journal-title":"Cell Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1172\/JCI23621","article-title":"Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease","volume":"115","author":"Donnelly","year":"2005","journal-title":"J. Clin. Invest."},{"key":"ref_39","first-page":"747","article-title":"Fatty acid synthase and liver triglyceride metabolism: Housekeeper or messenger?","volume":"1821","author":"Semenkovich","year":"2012","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1002\/hep.28415","article-title":"Acetyl-coenzyme A carboxylase alpha promotion of glucose-mediated fatty acid synthesis enhances survival of hepatocellular carcinoma in mice and patients","volume":"63","author":"Wang","year":"2016","journal-title":"Hepatology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5762","DOI":"10.3390\/ijms15045762","article-title":"Fatty acid elongation in non-alcoholic steatohepatitis and hepatocellular carcinoma","volume":"15","author":"Kessler","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1053\/j.gastro.2013.01.054","article-title":"Integrated metabolite and gene expression profiles identify lipid biomarkers associated with progression of hepatocellular carcinoma and patient outcomes","volume":"144","author":"Budhu","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jhep.2021.02.027","article-title":"Fructose- and sucrose- but not glucose-sweetened beverages promote hepatic de novo lipogenesis: A randomized controlled trial","volume":"75","author":"Hochuli","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1007\/s10620-016-4054-0","article-title":"Role of Dietary Fructose and Hepatic De Novo Lipogenesis in Fatty Liver Disease","volume":"61","author":"Softic","year":"2016","journal-title":"Dig. Dis. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1093\/embo-reports\/kve071","article-title":"Mechanisms of nutritional and hormonal regulation of lipogenesis","volume":"2","author":"Kersten","year":"2001","journal-title":"EMBO Rep."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Iizuka, K., Takao, K., and Yabe, D. (2020). ChREBP-mediated regulation of lipid metabolism: Involvement of the gut microbiota, liver, and adipose tissue. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.587189"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.hbpd.2020.05.010","article-title":"ATP-citrate lyase regulates stemness and metastasis in hepatocellular carcinoma via the Wnt\/\u03b2-catenin signaling pathway","volume":"20","author":"Han","year":"2021","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1186\/s12935-020-01520-4","article-title":"NONO promotes hepatocellular carcinoma progression by enhancing fatty acids biosynthesis through interacting with ACLY mRNA","volume":"20","author":"Ding","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1002\/mc.23777","article-title":"ATP citrate lyase promotes the progression of hepatocellular carcinoma by activating the REG\u03b3-proteasome pathway","volume":"63","author":"Cai","year":"2024","journal-title":"Mol. Carcinog."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1186\/s12935-021-02108-2","article-title":"Identification and integrative analysis of ACLY and related gene panels associated with immune microenvironment reveal prognostic significance in hepatocellular carcinoma","volume":"21","author":"Xu","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"14689","DOI":"10.1038\/ncomms14689","article-title":"Inhibition of hepatic lipogenesis enhances liver tumorigenesis by increasing antioxidant defence and promoting cell survival","volume":"8","author":"Nelson","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s40170-024-00363-1","article-title":"Complete inhibition of liver acetyl-CoA carboxylase activity is required to exacerbate liver tumorigenesis in mice treated with diethylnitrosamine","volume":"12","author":"Shrestha","year":"2024","journal-title":"Cancer Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.molmet.2014.02.004","article-title":"Genetic inhibition of hepatic acetyl-CoA carboxylase activity increases liver fat and alters global protein acetylation","volume":"3","author":"Chow","year":"2014","journal-title":"Mol. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.jhep.2020.04.037","article-title":"Acetyl-CoA carboxylase inhibition disrupts metabolic reprogramming during hepatic stellate cell activation","volume":"73","author":"Bates","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.jhep.2015.10.004","article-title":"Inactivation of fatty acid synthase impairs hepatocarcinogenesis driven by AKT in mice and humans","volume":"64","author":"Li","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1136\/gutjnl-2018-317581","article-title":"Cholesterol biosynthesis supports the growth of hepatocarcinoma lesions depleted of fatty acid synthase in mice and humans","volume":"69","author":"Che","year":"2020","journal-title":"Gut"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1038\/s41388-020-1156-0","article-title":"Stabilization of FASN by ACAT1-mediated GNPAT acetylation promotes lipid metabolism and hepatocarcinogenesis","volume":"39","author":"Gu","year":"2020","journal-title":"Oncogene"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Zhang, B., Zhou, B.H., Xiao, M., Li, H., Guo, L., Wang, M.X., and Yu, J. (2020). KDM5C represses FASN-mediated lipid metabolism to exert tumor suppressor activity in intrahepatic cholangiocarcinoma. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01025"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1093\/carcin\/23.11.1933","article-title":"Stearoyl-CoA desaturase 1 (Scd1) gene overexpression is associated with genetic predisposition to hepatocarcinogenesis in mice and rats","volume":"23","author":"Falvella","year":"2002","journal-title":"Carcinogenesis"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.canlet.2014.12.036","article-title":"SCD1 negatively regulates autophagy-induced cell death in human hepatocellular carcinoma through inactivation of the AMPK signaling pathway","volume":"358","author":"Huang","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/s41586-019-0904-1","article-title":"Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity","volume":"566","author":"Vriens","year":"2019","journal-title":"Nature"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"101491","DOI":"10.1016\/j.gendis.2024.101491","article-title":"Emerging roles for fatty acid oxidation in cancer","volume":"12","author":"Ma","year":"2025","journal-title":"Genes Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/s41420-025-02554-1","article-title":"The role and mechanism of fatty acid oxidation in cancer drug resistance","volume":"11","author":"Lei","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.cmet.2017.11.001","article-title":"JAK\/STAT3-regulated fatty acid \u03b2-oxidation is critical for breast cancer stem cell self-renewal and chemoresistance","volume":"27","author":"Wang","year":"2018","journal-title":"Cell Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1038\/s41467-022-29137-3","article-title":"Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion","volume":"13","author":"Jiang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ebiom.2016.11.025","article-title":"High Expression of CPT1A Predicts Adverse Outcomes: A Potential Therapeutic Target for Acute Myeloid Leukemia","volume":"14","author":"Shi","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1002\/hep.32088","article-title":"discovery of a carbamoyl phosphate synthetase 1\u2013deficient hcc subtype with therapeutic potential through integrative genomic and experimental analysis","volume":"74","author":"Wu","year":"2021","journal-title":"Hepatology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1136\/gutjnl-2017-315448","article-title":"\u03b2-catenin-activated hepatocellular carcinomas are addicted to fatty acids","volume":"68","author":"Senni","year":"2019","journal-title":"Gut"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.canlet.2018.08.006","article-title":"Fatty acid oxidation: An emerging facet of metabolic transformation in cancer","volume":"435","author":"Ma","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/cac2.12247","article-title":"Increased mitochondrial fission drives the reprogramming of fatty acid metabolism in hepatocellular carcinoma cells through suppression of Sirtuin 1","volume":"42","author":"Wu","year":"2022","journal-title":"Cancer Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40170-021-00276-3","article-title":"MicroRNA-377-3p inhibits hepatocellular carcinoma growth and metastasis through negative regulation of CPT1C-mediated fatty acid oxidation","volume":"10","author":"Zhang","year":"2022","journal-title":"Cancer Metab."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2874","DOI":"10.1158\/0008-5472.CAN-20-2052","article-title":"E2F1 and E2F2-mediated repression of CPT2 establishes a lipid-rich tumor-promoting environment","volume":"81","author":"Mestre","year":"2021","journal-title":"Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1136\/gutjnl-2017-315193","article-title":"CPT2 downregulation adapts HCC to lipid-rich environment and promotes carcinogenesis via acylcarnitine accumulation in obesity","volume":"67","author":"Fujiwara","year":"2018","journal-title":"Gut"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/s41419-021-03648-1","article-title":"Down-regulation of SLC25A20 promotes hepatocellular carcinoma growth and metastasis through suppression of fatty-acid oxidation","volume":"12","author":"Yuan","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1038\/s41418-019-0399-1","article-title":"SLC27A5 deficiency activates NRF2\/TXNRD1 pathway by increased lipid peroxidation in HCC","volume":"27","author":"Gao","year":"2020","journal-title":"Cell Death Differ."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.jhep.2023.08.029","article-title":"Bioactive signalling lipids as drivers of chronic liver diseases","volume":"80","author":"Kaffe","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"100479","DOI":"10.1016\/j.jhepr.2022.100479","article-title":"Lipid alterations in chronic liver disease and liver cancer","volume":"4","author":"Paul","year":"2022","journal-title":"JHEP Rep."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Liu, X., Liu, X., Shi, Q., Fan, X., and Qi, K. (2021). Association of telomere length and telomerase methylation with n-3 fatty acids in preschool children with obesity. BMC Pediatr., 21.","DOI":"10.1186\/s12887-020-02487-x"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/liv.13529","article-title":"Telomerase enzyme deficiency promotes metabolic dysfunction in murine hepatocytes upon dietary stress","volume":"38","author":"Kajigaya","year":"2018","journal-title":"Liver Int."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1136\/gutjnl-2014-308430","article-title":"MicroRNA-21 is a potential link between non-alcoholic fatty liver disease and hepatocellular carcinoma via modulation of the HBP1-p53-Srebp1c pathway","volume":"65","author":"Wu","year":"2016","journal-title":"Gut"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.tibs.2010.08.001","article-title":"Regulation of sphingosine kinase and sphingolipid signaling","volume":"36","author":"Pitson","year":"2011","journal-title":"Trends Biochem. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4149","DOI":"10.1038\/s41467-018-06650-y","article-title":"C16-ceramide is a natural regulatory ligand of p53 in cellular stress response","volume":"9","author":"Fekry","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1159\/000233248","article-title":"A Ceramide-binding C1 domain mediates kinase suppressor of Ras Membrane Translocation","volume":"24","author":"Yin","year":"2009","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"18095","DOI":"10.18632\/oncotarget.7741","article-title":"Serum sphingolipidomic analyses reveal an upregulation of C16-ceramide and sphingosine-1-phosphate in hepatocellular carcinoma","volume":"7","author":"Grammatikos","year":"2016","journal-title":"Oncotarget"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Uranbileg, B., Ikeda, H., Kurano, M., Enooku, K., Sato, M., Saigusa, D., Nagano, T., Hashimoto, N., Tsuruya, K., and Aoki, J. (2016). Increased mRNA levels of sphingosine kinases and S1P lyase and reduced levels of S1P were observed in hepatocellular carcinoma in association with poorer differentiation and earlier recurrence. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149462"},{"key":"ref_87","first-page":"2456","article-title":"Targeting the eicosanoid pathway in hepatocellular carcinoma","volume":"11","author":"Razdan","year":"2021","journal-title":"Am. J. Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1158\/0008-5472.CAN-14-2561","article-title":"Omega-3 polyunsaturated fatty acids upregulate 15-pgdh expression in cholangiocarcinoma cells by inhibiting miR-26a\/b expression","volume":"75","author":"Yao","year":"2015","journal-title":"Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.5114\/aoms.2016.61916","article-title":"Prognostic signifcance of cyclooxygenase-2 expression in patients with hepatocellular carcinoma: A meta-analysis","volume":"12","author":"Chen","year":"2016","journal-title":"Arch. Med. Sci."},{"key":"ref_90","first-page":"1410","article-title":"Expression of cyclooxygenase-2 (COX-2) in hepatocellular carcinoma and growth inhibition of hepatoma cell lines by a COX-2 inhibitor, NS-398","volume":"7","author":"Bae","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1093\/carcin\/bgh110","article-title":"Cyclooxygenase-2 inhibitors suppress the growth of human hepatocellular carcinoma implants in nude mice","volume":"25","author":"Kern","year":"2004","journal-title":"Carcinogenesis"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1002\/stem.2821","article-title":"PGD2\/PTGDR2 signaling restricts the self-renewal and tumorigenesis of gastric cancer","volume":"36","author":"Zhang","year":"2018","journal-title":"Stem Cells"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/sj.cdd.4400908","article-title":"Lipoxygenases and their involvement in programmed cell death","volume":"8","author":"Maccarrone","year":"2001","journal-title":"Cell Death Differ."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"114592","DOI":"10.1016\/j.biopha.2023.114592","article-title":"Hepatocellular carcinoma progression promoted by 5-lipoxygenase activity in CD163(+) tumor-associated macrophages","volume":"162","author":"Nosaka","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.smim.2017.09.005","article-title":"The yin and yang of leukotriene B4 mediated inflammation in cancer","volume":"33","author":"Jala","year":"2017","journal-title":"Semin. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1038\/s41388-024-03016-1","article-title":"The role of human 5-Lipoxygenase (5-LO) in carcinogenesis\u2014A question of canonical and non-canonical functions","volume":"43","author":"Kahnt","year":"2024","journal-title":"Oncogene"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jss.2009.09.005","article-title":"Hepatocellular carcinoma associated lipid metabolism reprogramming","volume":"169","author":"Skill","year":"2011","journal-title":"J. Surg. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"66154","DOI":"10.18632\/oncotarget.19825","article-title":"EDG2 enhanced the progression of hepatocellular carcinoma by LPA\/PI3K\/AKT\/mTOR signaling","volume":"8","author":"Xu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Cigliano, A., Simile, M.M., Vidili, G., Pes, G.M., Dore, M.P., Urigo, F., Cossu, E., Che, L., Feo, C., and Steinmann, S.M. (2024). Fatty acid synthase promotes hepatocellular carcinoma growth via S-phase kinase-associated protein 2\/p27kip1 regulation. Medicina, 60.","DOI":"10.3390\/medicina60071160"},{"key":"ref_100","first-page":"785","article-title":"Lysophosphatidic acid enhances human hepatocellular carcinoma cell migration, invasion and adhesion through P38 MAPK pathway","volume":"59","author":"Zhu","year":"2012","journal-title":"Hepatogastroenterology"},{"key":"ref_101","first-page":"481","article-title":"Phosphatidylcholine induces growth inhibition of hepatic cancer by apoptosis via death ligands","volume":"56","author":"Sakakima","year":"2009","journal-title":"Hepatogastroenterology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1177\/1074248411424145","article-title":"Thromboxane A2 Receptor: Biology and Function of a Peculiar Receptor that Remains Resistant for Therapeutic Targeting","volume":"17","author":"Ting","year":"2011","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"5922","DOI":"10.1021\/cr100396c","article-title":"Resolvins and protectins in inflammation resolution","volume":"111","author":"Serhan","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_104","first-page":"181","article-title":"Lipoxins: Nature\u2019s way to resolve inflammation","volume":"8","author":"Chandrasekharan","year":"2015","journal-title":"J. Inflamm. Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature13479","article-title":"Pro-resolving lipid mediators are leads for resolution physiology","volume":"510","author":"Serhan","year":"2014","journal-title":"Nature"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0163-7827(99)00016-8","article-title":"Platelet-activating factor (PAF) receptor and genetically engineered PAF receptor mutant mice","volume":"39","author":"Ishii","year":"2000","journal-title":"Prog. Lipid Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"8117","DOI":"10.1158\/0008-5472.CAN-09-3871","article-title":"De novo lipogenesis protects cancer cells from free radicals and chemotherapeutics by promoting membrane lipid saturation","volume":"70","author":"Rysman","year":"2010","journal-title":"Cancer Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1158\/0008-5472.CAN-15-1970","article-title":"Candidate antimetastasis drugs suppress the metastatic capacity of breast cancer cells by reducing membrane fluidity","volume":"76","author":"Zhao","year":"2016","journal-title":"Cancer Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"25661","DOI":"10.18632\/oncotarget.25432","article-title":"Altered membrane rigidity via enhanced endogenous cholesterol synthesis drives cancer cell resistance to destruxins","volume":"9","author":"Heilos","year":"2018","journal-title":"Oncotarget"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1016\/j.ymthe.2022.03.015","article-title":"An SCD1-dependent mechanoresponsive pathway promotes HCC invasion and metastasis through lipid metabolic reprogramming","volume":"30","author":"Liu","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1002\/hep.29033","article-title":"Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism","volume":"66","author":"Lin","year":"2017","journal-title":"Hepatology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e008811","DOI":"10.1136\/jitc-2024-008811","article-title":"Harnessing lipid metabolism modulation for improved immunotherapy outcomes in lung adenocarcinoma","volume":"12","author":"Chen","year":"2024","journal-title":"J. Immunother. Cancer"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1096\/fj.201800985R","article-title":"CD36-triggered cell invasion and persistent tissue colonization by tumor microvesicles during metastasis","volume":"33","author":"Pfeiler","year":"2019","journal-title":"FASEB J."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1158\/0008-5472.CAN-23-4027","article-title":"Scavenger receptor CD36 in tumor-associated macrophages promotes cancer progression by dampening type-I IFN signaling","volume":"85","author":"Xu","year":"2025","journal-title":"Cancer Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1158\/2326-6066.CIR-19-0261","article-title":"RIPK3 orchestrates fatty acid metabolism in tumor-associated macrophages and hepatocarcinogenesis","volume":"8","author":"Wu","year":"2020","journal-title":"Cancer Immunol. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e002548","DOI":"10.1136\/jitc-2021-002548","article-title":"S100A4 enhances protumor macrophage polarization by control of PPAR-\u03b3-dependent induction of fatty acid oxidation","volume":"9","author":"Liu","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/nature14011","article-title":"Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients","volume":"515","author":"Herbst","year":"2014","journal-title":"Nature"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1038\/s41417-022-00510-0","article-title":"Lipid-related FABP5 activation of tumor-associated monocytes fosters immune privilege via PD-L1 expression on Treg cells in hepatocellular carcinoma","volume":"29","author":"Liu","year":"2022","journal-title":"Cancer Gene Ther."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/hep.32573","article-title":"Multiomics identifies the link between intratumor steatosis and the exhausted tumor immune microenvironment in hepatocellular carcinoma","volume":"77","author":"Murai","year":"2023","journal-title":"Hepatology"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3800","DOI":"10.1096\/fj.201600522R","article-title":"The AMP analog AICAR modulates the Treg\/Th17 axis through enhancement of fatty acid oxidation","volume":"30","author":"Gualdoni","year":"2016","journal-title":"FASEB J."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Chen, L., Zhou, Q., Liu, J., and Zhang, W. (2021). CTNNB1 alternation is a potential biomarker for immunotherapy prognosis in patients with hepatocellular carcinoma. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.759565"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1038\/s41467-021-22967-7","article-title":"Targeting human Acyl-CoA:cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint","volume":"12","author":"Schmidt","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Tiwary, S., Berzofsky, J.A., and Terabe, M. (2019). Altered lipid tumor environment and its potential effects on NKT cell function in tumor immunity. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02187"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/s41423-022-00872-3","article-title":"Aberrant cholesterol metabolic signaling impairs antitumor immunosurveillance through natural killer T cell dysfunction in obese liver","volume":"19","author":"Tang","year":"2022","journal-title":"Cell. Mol. Immunol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1016\/j.cell.2020.11.009","article-title":"Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity","volume":"183","author":"Ringel","year":"2020","journal-title":"Cell"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1038\/s41590-020-0769-3","article-title":"The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies","volume":"21","author":"Kumagai","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1158\/0008-5472.CAN-22-2273","article-title":"Long-chain acylcarnitines induce senescence of invariant natural killer T cells in hepatocellular carcinoma","volume":"83","author":"Cheng","year":"2023","journal-title":"Cancer Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1093\/jleuko\/qiad081","article-title":"Lipid metabolism in the immune niche of tumor-prone liver microenvironment","volume":"115","author":"Chen","year":"2024","journal-title":"J. Leukoc. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Oliviero, B., Caretti, A., Mondelli, M.U., and Mantovani, S. (2025). Lipid Metabolism Reprogramming in Tumor-Associated Macrophages Modulates Their Function in Primary Liver Cancers. Cancers, 17.","DOI":"10.3390\/cancers17111858"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Pascual, G., and Benitah, S.A. (2024). Lipids in the tumor microenvironment: Immune modulation and metastasis. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1435480"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/s41420-025-02397-w","article-title":"New insights into T cell metabolism in liver cancer: From mechanism to therapy","volume":"11","author":"Xiao","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Wang, D., Ye, Q., Gu, H., and Chen, Z. (2022). The role of lipid metabolism in tumor immune microenvironment and potential therapeutic strategies. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.984560"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Zhou, L., Zhang, W., Liu, Z., Xie, Y., and Jiang, K. (2025). Immune cell metabolic reprogramming in hepatocellular carcinoma: Mechanisms, tumor microenvironment, and future immunotherapeutic directions. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1697675"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Fan, C., Kam, S., and Ramadori, P. (2021). Metabolism-associated epigenetic and immunoepigenetic reprogramming in liver cancer. Cancers, 13.","DOI":"10.3390\/cancers13205250"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Li, A., Wang, R., Zhao, Y., Zhao, P., and Yang, J. (2024). Crosstalk between epigenetics and metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease-induced hepatocellular carcinoma: A new sight. Metabolites, 14.","DOI":"10.3390\/metabo14060325"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1126\/science.1164097","article-title":"ATP-citrate lyase links cellular metabolism to histone acetylation","volume":"324","author":"Wellen","year":"2009","journal-title":"Science"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.celrep.2016.09.069","article-title":"ATP-citrate lyase controls a glucose-to-acetate metabolic switch","volume":"17","author":"Zhao","year":"2016","journal-title":"Cell Rep."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.cmet.2014.06.004","article-title":"Akt-dependent metabolic reprogramming regulates tumor cell Histone acetylation","volume":"20","author":"Lee","year":"2014","journal-title":"Cell Metab."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/nrc.2016.87","article-title":"The metabolic fate of acetate in cancer","volume":"16","author":"Schug","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s13046-023-02656-7","article-title":"Activation of ACLY by SEC63 deploys metabolic reprogramming to facilitate hepatocellular carcinoma metastasis upon endoplasmic reticulum stress","volume":"42","author":"Hu","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1126\/science.1227166","article-title":"Suppression of oxidative stress by \u03b2-hydroxybutyrate, an endogenous histone deacetylase inhibitor","volume":"339","author":"Shimazu","year":"2013","journal-title":"Science"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.molcel.2016.03.036","article-title":"Metabolic regulation of gene expression by histone lysine \u03b2-Hydroxybutyrylation","volume":"62","author":"Xie","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/nrc.2016.82","article-title":"Metabolic control of epigenetics in cancer","volume":"16","author":"Kinnaird","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.canlet.2017.12.035","article-title":"SIRT1 and HIF1\u03b1 signaling in metabolism and immune responses","volume":"418","author":"Yu","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1136\/gutjnl-2019-318918","article-title":"Targeting clinical epigenetic reprogramming for chemoprevention of metabolic and viral hepatocellular carcinoma","volume":"70","author":"Hamdane","year":"2021","journal-title":"Gut"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"100127","DOI":"10.1016\/j.crbiot.2023.100127","article-title":"CRISPR\/Cas9 genetic screens in hepatocellular carcinoma gene discovery","volume":"5","author":"Chiu","year":"2023","journal-title":"Curr. Res. Biotechnol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13148-023-01482-0","article-title":"Epigenetic reactivation of tumor suppressor genes with CRISPRa technologies as precision therapy for hepatocellular carcinoma","volume":"15","author":"Sgro","year":"2023","journal-title":"Clin. Epigenetics"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cell.2009.11.027","article-title":"Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis","volume":"140","author":"Nomura","year":"2010","journal-title":"Cell"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1139\/O07-001","article-title":"Upregulation of cellular triacylglycerol\u2014Free fatty acid cycling by oleate is associated with long-term serum-free survival of human breast cancer cells","volume":"85","author":"Przybytkowski","year":"2007","journal-title":"Biochem. Cell Biol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s10565-025-10098-4","article-title":"Lipolysis gone rogue: The HSL connection in feeding cancer","volume":"41","author":"Hemadri","year":"2025","journal-title":"Cell Biol. Toxicol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"35784","DOI":"10.1038\/srep35784","article-title":"Monoacylglycerol lipase: A novel potential therapeutic target and prognostic indicator for hepatocellular carcinoma","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Han, P., Wang, H., Chen, Y., Ge, Y., Xu, H., Ren, H., and Meng, Y. (2025). The role of lipophagy in liver cancer: Mechanisms and targeted therapeutic interventions. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1562542"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2147\/JHC.S450423","article-title":"Lipid metabolism as a potential target of liver cancer","volume":"11","author":"Wu","year":"2024","journal-title":"J. Hepatocell. Carcinoma"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s43018-020-00168-3","article-title":"LXR\u03b1 activation and Raf inhibition trigger lethal lipotoxicity in liver cancer","volume":"2","author":"Rudalska","year":"2021","journal-title":"Nat. Cancer"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41580-018-0085-z","article-title":"Dynamics and functions of lipid droplets","volume":"20","author":"Olzmann","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Petan, T., Jarc, E., and Jusovic, M. (2018). Lipid droplets in cancer: Guardians of fat in a stressful world. Molecules, 23.","DOI":"10.3390\/molecules23081941"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.bbalip.2017.12.006","article-title":"Lipid droplets induced by secreted phospholipase A2 and unsaturated fatty acids protect breast cancer cells from nutrient and lipotoxic stress","volume":"1863","author":"Jarc","year":"2018","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"eabo2510","DOI":"10.1126\/sciadv.abo2510","article-title":"Lipid droplet turnover at the lysosome inhibits growth of hepatocellular carcinoma in a BNIP3-dependent manner","volume":"8","author":"Berardi","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.canlet.2020.12.019","article-title":"ACSL4 reprograms fatty acid metabolism in hepatocellular carcinoma via c-Myc\/SREBP1 pathway","volume":"502","author":"Chen","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_160","first-page":"3485","article-title":"Hypoxia causes triglyceride accumulation by hif-1-mediated stimulation of lipin 1 expression","volume":"125","author":"Mylonis","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.cmet.2018.08.020","article-title":"Inhibition of acetyl-CoA carboxylase by phosphorylation or the inhibitor ND-654 suppresses lipogenesis and hepatocellular carcinoma","volume":"29","author":"Lally","year":"2019","journal-title":"Cell Metab."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1002\/hep.30097","article-title":"Acetyl-CoA carboxylase inhibition reverses NAFLD and hepatic insulin resistance but promotes hypertriglyceridemia in rodents","volume":"68","author":"Goedeke","year":"2018","journal-title":"Hepatology"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1080\/13543784.2020.1668374","article-title":"GS-0976 (Firsocostat): An investigational liver-directed acetyl-CoA carboxylase (ACC) inhibitor for the treatment of non-alcoholic steatohepatitis (NASH)","volume":"29","author":"Alkhouri","year":"2020","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/hep.31622","article-title":"Combination therapies including cilofexor and firsocostat for bridging fibrosis and cirrhosis attributable to NASH","volume":"73","author":"Loomba","year":"2021","journal-title":"Hepatology"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"e056159","DOI":"10.1136\/bmjopen-2021-056159","article-title":"Efficacy and safety of an orally administered DGAT2 inhibitor alone or coadministered with a liver-targeted ACC inhibitor in adults with non-alcoholic steatohepatitis (NASH): Rationale and design of the phase II, dose-ranging, dose-finding, randomised, placebo-controlled MIRNA (Metabolic Interventions to Resolve NASH with fibrosis) study","volume":"12","author":"Amin","year":"2022","journal-title":"BMJ Open"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1038\/s41591-021-01489-1","article-title":"ACC inhibitor alone or co-administered with a DGAT2 inhibitor in patients with non-alcoholic fatty liver disease: Two parallel, placebo-controlled, randomized phase 2a trials","volume":"27","author":"Calle","year":"2021","journal-title":"Nat. Med."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"e011662","DOI":"10.1161\/JAHA.118.011662","article-title":"Efficacy and safety of bempedoic acid in patients with hypercholesterolemia and statin intolerance","volume":"8","author":"Laufs","year":"2019","journal-title":"J. Am. Heart Assoc."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1001\/jamacardio.2020.2314","article-title":"Association of bempedoic acid administration with atherogenic lipid levels in phase 3 randomized clinical trials of patients with hypercholesterolemia","volume":"5","author":"Banach","year":"2020","journal-title":"JAMA Cardiol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"e024531","DOI":"10.1161\/JAHA.121.024531","article-title":"Factors associated with enhanced low-density lipoprotein cholesterol lowering with bempedoic acid","volume":"11","author":"Ballantyne","year":"2022","journal-title":"J. Am. Heart Assoc."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"13457","DOI":"10.1038\/ncomms13457","article-title":"Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis","volume":"7","author":"Pinkosky","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/hep.31249","article-title":"The IKK\u03b2-USP30-ACLY axis controls lipogenesis and tumorigenesis","volume":"73","author":"Gu","year":"2021","journal-title":"Hepatology"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"978","DOI":"10.4161\/cbt.5.8.2883","article-title":"Growth arrest induced by C75, a fatty acid synthase inhibitor, was partially modulated by p38 MAPK but not by p53 in human hepatocellular carcinoma","volume":"5","author":"Gao","year":"2006","journal-title":"Cancer Biol. Ther."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"100660","DOI":"10.1016\/j.jlr.2024.100660","article-title":"Fatty acid synthase inhibitor cerulenin hinders liver cancer stem cell properties through FASN\/APP axis as novel therapeutic strategies","volume":"65","author":"Chen","year":"2024","journal-title":"J. Lipid Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"5434","DOI":"10.1158\/1078-0432.CCR-15-0126","article-title":"Molecular pathways: Fatty acid synthase","volume":"21","author":"Jones","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"114918","DOI":"10.1016\/j.taap.2020.114918","article-title":"Orlistat delays hepatocarcinogenesis in mice with hepatic co-activation of AKT and c-Met","volume":"392","author":"Zhang","year":"2020","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1021\/acs.chemrestox.8b00269","article-title":"Orlistat displays antitumor activity and enhances the efficacy of paclitaxel in human hepatoma Hep3B cells","volume":"32","author":"You","year":"2019","journal-title":"Chem. Res. Toxicol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"11355","DOI":"10.1096\/fj.202000705R","article-title":"Inhibitors of lipogenic enzymes as a potential therapy against cancer","volume":"34","author":"Montesdeoca","year":"2020","journal-title":"FASEB J."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"100797","DOI":"10.1016\/j.eclinm.2021.100797","article-title":"First-in-human study of the safety, pharmacokinetics, and pharmacodynamics of first-in-class fatty acid synthase inhibitor TVB-2640 alone and with a taxane in advanced tumors","volume":"34","author":"Falchook","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/S2468-1253(24)00246-2","article-title":"Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis: A multicentre, double-blind, randomised, placebo-controlled, phase 2b trial","volume":"9","author":"Loomba","year":"2024","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/S2468-1253(24)00306-6","article-title":"Expanding the armamentarium for metabolic dysfunction-associated steatohepatitis","volume":"9","author":"Francque","year":"2024","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"4642","DOI":"10.1158\/1078-0432.CCR-16-2363","article-title":"A phase I study of ABC294640, a first-in-class sphingosine kinase-2 inhibitor, in patients with advanced solid tumors","volume":"23","author":"Britten","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"20080","DOI":"10.18632\/oncotarget.7914","article-title":"Antitumor effect of the novel sphingosine kinase 2 inhibitor ABC294640 is enhanced by inhibition of autophagy and by sorafenib in human cholangiocarcinoma cells","volume":"7","author":"Ding","year":"2016","journal-title":"Oncotarget"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1124\/jpet.109.163337","article-title":"A novel sphingosine kinase inhibitor induces autophagy in tumor cells","volume":"333","author":"Beljanski","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1124\/jpet.109.163444","article-title":"Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2","volume":"333","author":"French","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.jhep.2017.06.015","article-title":"Stearoyl-CoA desaturase regulates sorafenib resistance via modulation of ER stress-induced differentiation","volume":"67","author":"Ma","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.canlet.2018.10.024","article-title":"Diet-induced hepatic steatosis activates Ras to promote hepatocarcinogenesis via CPT1\u03b1","volume":"442","author":"Xu","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s41420-021-00504-1","article-title":"Simultaneously targeting SOAT1 and CPT1A ameliorates hepatocellular carcinoma by disrupting lipid homeostasis","volume":"7","author":"Ren","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"102300","DOI":"10.1016\/j.eclinm.2023.102300","article-title":"Association between statin use and the prognosis of hepatocellular carcinoma after resection: A nationwide cohort study","volume":"65","author":"Jeon","year":"2023","journal-title":"EClinicalMedicine"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1001\/jamainternmed.2025.0115","article-title":"Statin use and risk of hepatocellular carcinoma and liver fibrosis in chronic liver disease","volume":"185","author":"Choi","year":"2025","journal-title":"JAMA Intern. Med."},{"key":"ref_190","first-page":"943","article-title":"Association between blood lipid levels and the risk of liver cancer: A systematic review and meta-analysis","volume":"35","author":"Zhang","year":"2024","journal-title":"Cancer Causes Control"},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Zeng, C., Liu, S., Li, H., and Han, X. (2025). Inverse association between serum lipid profiles and hepatocellular carcinoma risk: A meta-analysis of epidemiological studies. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1644677"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"e32113","DOI":"10.1016\/j.heliyon.2024.e32113","article-title":"Serum high-density lipoprotein cholesterol levels predict early recurrence and prognosis of intrahepatic cholangiocarcinoma after surgical resection","volume":"10","author":"Yu","year":"2024","journal-title":"Heliyon"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"100627","DOI":"10.1016\/j.jhepr.2022.100627","article-title":"Low HDL-cholesterol levels predict hepatocellular carcinoma development in individuals with liver fibrosis","volume":"5","author":"Crudele","year":"2023","journal-title":"JHEP Rep."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1177\/1724600818776838","article-title":"Plasma cholesterol and lipoprotein levels in relation to tumor aggressiveness and survival in HCC patients","volume":"33","author":"Carr","year":"2018","journal-title":"Int. J. Biol. Markers"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/jssc.201700709","article-title":"Mass-spectrometry-based lipidomics","volume":"41","author":"Hu","year":"2018","journal-title":"J. Sep. Sci."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s00216-012-5782-4","article-title":"Serum metabolomics reveals the deregulation of fatty acids metabolism in hepatocellular carcinoma and chronic liver diseases","volume":"403","author":"Zhou","year":"2012","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1002\/hep.21763","article-title":"A lipidomic analysis of nonalcoholic fatty liver disease","volume":"46","author":"Puri","year":"2007","journal-title":"Hepatology"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1002\/hep.23229","article-title":"The plasma lipidomic signature of nonalcoholic steatohepatitis","volume":"50","author":"Puri","year":"2009","journal-title":"Hepatology"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"4722","DOI":"10.1158\/0008-5472.CAN-12-3797","article-title":"Proteomic and lipidomic signatures of lipid metabolism in NASH-associated Hepatocellular carcinoma","volume":"73","author":"Muir","year":"2013","journal-title":"Cancer Res."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"5536","DOI":"10.7150\/jca.48495","article-title":"Reduction of polyunsaturated fatty acids with tumor progression in a lean non-alcoholic steatohepatitis-associated hepatocellular carcinoma mouse model","volume":"11","author":"Vlock","year":"2020","journal-title":"J. Cancer"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"103661","DOI":"10.1016\/j.ebiom.2021.103661","article-title":"The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma: Diagnosis of NAFLD-HCC utilising serum lipidomics","volume":"73","author":"Lewinska","year":"2021","journal-title":"EBioMedicine"},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Li, Z., Guan, M., Lin, Y., Cui, X., Zhang, Y., Zhao, Z., and Zhu, J. (2017). Aberrant lipid metabolism in hepatocellular carcinoma revealed by liver lipidomics. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122550"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"6590","DOI":"10.1158\/0008-5472.CAN-11-0885","article-title":"Aberrant lipid metabolism in hepatocellular carcinoma revealed by plasma metabolomics and lipid profiling","volume":"71","author":"Patterson","year":"2011","journal-title":"Cancer Res."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1186\/s40001-023-01523-7","article-title":"A comprehensive review of the family of very-long-chain fatty acid elongases: Structure, function, and implications in physiology and pathology","volume":"28","author":"Wang","year":"2023","journal-title":"Eur. J. Med. Res."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1093\/jb\/mvs105","article-title":"Very long-chain fatty acids: Elongation, physiology and related disorders","volume":"152","author":"Kihara","year":"2012","journal-title":"J. Biochem."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.jhep.2013.02.030","article-title":"Lysophosphatidylcholine acyltransferase 1 altered phospholipid composition and regulated hepatoma progression","volume":"59","author":"Morita","year":"2013","journal-title":"J. Hepatol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/2\/329\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T05:24:38Z","timestamp":1771737878000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/2\/329"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,20]]},"references-count":206,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["biom16020329"],"URL":"https:\/\/doi.org\/10.3390\/biom16020329","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,20]]}}}