{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:38:34Z","timestamp":1792193914506,"version":"4.4.0"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"FSC European funds","award":["C37G22000400001"],"award-info":[{"award-number":["C37G22000400001"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Non-alcoholic Fatty Liver Disease (NAFLD), now better known as Metabolic (Dysfunction)-Associated Fatty Liver Disease (MAFLD) and its progression to Nonalcoholic Steatohepatitis (NASH), more recently referred to as Metabolic (Dysfunction)-Associated Steatohepatitis (MASH) are the most common causes of liver failure and chronic liver damage. The new names emphasize the metabolic involvement both in relation to liver function and pathological features with extrahepatic manifestations. This study aims to explore the role of the immunometabolic enzyme ATP citrate lyase (ACLY), with a critical function in lipogenesis, carbohydrate metabolism, gene expression and inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>ACLY function was investigated in TNF\u03b1-triggered human hepatocytes and in PBMC-derived macrophages from MASH patients. Evaluation of expression levels was carried out by western blotting and\/or RT-qPCR. In the presence or absence of ACLY inhibitors, ROS, lipid peroxidation and GSSG oxidative stress biomarkers were quantified. Chromatin immunoprecipitation (ChIP), transient transfections, immunocytochemistry, histone acetylation quantitation were used to investigate ACLY function in gene expression reprogramming. IL-6 and IL-1\u03b2 were quantified by Lumit immunoassays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mechanistically, ACLY inhibition reverted lipid accumulation and oxidative damage while reduced secretion of inflammatory cytokines in TNF\u03b1-triggered human hepatocytes. These effects impacted not only on lipid metabolism but also on other crucial features of liver function such as redox status and production of inflammatory mediators. Moreover, ACLY mRNA levels together with those of malic enzyme 1 (ME1) increased in human PBMC-derived macrophages from MASH patients when compared to age-matched healthy controls. Remarkably, a combination of hydroxycitrate (HCA), the natural ACLY inhibitor, with red wine powder (RWP) significantly lowered ACLY and ME1 mRNA amount as well as IL-6 and IL-1\u03b2 production in macrophages from subjects with MASH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, our findings for the first time highlight a broad spectrum of ACLY functions in liver as well as in the pathogenesis of MASH and its diagnostic and therapeutic potential value.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-023-04431-w","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T14:03:02Z","timestamp":1692885782000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["ACLY as a modulator of liver cell functions and its role in Metabolic Dysfunction-Associated Steatohepatitis"],"prefix":"10.1186","volume":"21","author":[{"given":"Paolo","family":"Convertini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Santarsiero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Todisco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Gilio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Palazzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Pappalardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominga","family":"Iacobazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Frontuto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8509-5218","authenticated-orcid":false,"given":"Vittoria","family":"Infantino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,24]]},"reference":[{"issue":"1","key":"4431_CR1","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","volume":"73","author":"M Eslam","year":"2020","unstructured":"Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M, et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. J Hepatol. 2020;73(1):202\u20139.","journal-title":"J Hepatol"},{"key":"4431_CR2","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.2147\/DMSO.S369824","volume":"15","author":"QX Wang","year":"2022","unstructured":"Wang QX, Xue J, Shi MJ, Xie YB, Xiao HM, Li S, et al. Association between metabolic dysfunction-associated fatty liver disease and the risk of cirrhosis in patients with chronic hepatitis B\u2014a retrospective cohort study. Diabetes Metab Syndr Obes. 2022;15:2311\u201322.","journal-title":"Diabetes Metab Syndr Obes"},{"issue":"3","key":"4431_CR3","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.cgh.2021.11.038","volume":"21","author":"GEH Lim","year":"2023","unstructured":"Lim GEH, Tang A, Ng CH, Chin YH, Lim WH, Tan DJH, et al. An observational data meta-analysis on the differences in prevalence and risk factors between MAFLD vs NAFLD. Clin Gastroenterol Hepatol. 2023;21(3):619-629.e7.","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"2","key":"4431_CR4","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/liv.15139","volume":"42","author":"I Ayada","year":"2022","unstructured":"Ayada I, van Kleef LA, Alferink LJM, Li P, de Knegt RJ, Pan Q. Systematically comparing epidemiological and clinical features of MAFLD and NAFLD by meta-analysis: focusing on the non-overlap groups. Liver Int. 2022;42(2):277\u201387.","journal-title":"Liver Int"},{"issue":"9","key":"4431_CR5","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1210\/clinem\/dgac321","volume":"107","author":"KE Chan","year":"2022","unstructured":"Chan KE, Koh TJL, Tang ASP, Quek J, Yong JN, Tay P, et al. Global prevalence and clinical characteristics of metabolic-associated fatty liver disease: a meta-analysis and systematic review of 10 739 607 individuals. J Clin Endocrinol Metab. 2022;107(9):2691\u2013700.","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"4431_CR6","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.cmet.2017.07.008","volume":"26","author":"N Stefan","year":"2017","unstructured":"Stefan N, Schick F, Haring HU. Causes, characteristics, and consequences of metabolically unhealthy normal weight in humans. Cell Metab. 2017;26(2):292\u2013300.","journal-title":"Cell Metab"},{"issue":"2","key":"4431_CR7","doi-asserted-by":"crossref","first-page":"e745","DOI":"10.1210\/clinem\/dgab644","volume":"107","author":"X Wang","year":"2022","unstructured":"Wang X, Wu S, Yuan X, Chen S, Fu Q, Sun Y, et al. Metabolic dysfunction-associated fatty liver disease and mortality among Chinese adults: a prospective cohort study. J Clin Endocrinol Metab. 2022;107(2):e745\u201355.","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"4431_CR8","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.201809302","volume":"11","author":"AA Kolodziejczyk","year":"2019","unstructured":"Kolodziejczyk AA, Zheng D, Shibolet O, Elinav E. The role of the microbiome in NAFLD and NASH. EMBO Mol Med. 2019;11(2): e9302.","journal-title":"EMBO Mol Med"},{"key":"4431_CR9","volume":"12","author":"L Xu","year":"2021","unstructured":"Xu L, Liu W, Bai F, Xu Y, Liang X, Ma C, et al. Hepatic macrophage as a key player in fatty liver disease. Front Immunol. 2021;12: 708978.","journal-title":"Front Immunol"},{"issue":"6","key":"4431_CR10","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1085\/jgp.8.6.519","volume":"8","author":"O Warburg","year":"1927","unstructured":"Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol. 1927;8(6):519\u201330.","journal-title":"J Gen Physiol"},{"issue":"9","key":"4431_CR11","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/nri.2016.70","volume":"16","author":"LA O'Neill","year":"2016","unstructured":"O\u2019Neill LA, Kishton RJ, Rathmell J. A guide to immunometabolism for immunologists. Nat Rev Immunol. 2016;16(9):553\u201365.","journal-title":"Nat Rev Immunol"},{"key":"4431_CR12","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3389\/fimmu.2018.00141","volume":"9","author":"NC Williams","year":"2018","unstructured":"Williams NC, O\u2019Neill LAJ. A role for the krebs cycle intermediate citrate in metabolic reprogramming in innate immunity and inflammation. Front Immunol. 2018;9:141.","journal-title":"Front Immunol"},{"issue":"2","key":"4431_CR13","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.cell.2016.08.064","volume":"167","author":"EL Mills","year":"2016","unstructured":"Mills EL, Kelly B, Logan A, Costa ASH, Varma M, Bryant CE, et al. Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages. Cell. 2016;167(2):457-470.e13.","journal-title":"Cell"},{"issue":"40","key":"4431_CR14","doi-asserted-by":"crossref","first-page":"7104","DOI":"10.2174\/0929867325666180510124558","volume":"26","author":"V Infantino","year":"2019","unstructured":"Infantino V, Pierri CL, Iacobazzi V. Metabolic routes in inflammation: the citrate pathway and its potential as therapeutic target. Curr Med Chem. 2019;26(40):7104\u201316.","journal-title":"Curr Med Chem"},{"issue":"6","key":"4431_CR15","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.immuni.2019.11.009","volume":"51","author":"MA Lauterbach","year":"2019","unstructured":"Lauterbach MA, Hanke JE, Serefidou M, Mangan MSJ, Kolbe CC, Hess T, et al. Toll-like receptor signaling rewires macrophage metabolism and promotes histone acetylation via ATP-citrate lyase. Immunity. 2019;51(6):997-1011.e7.","journal-title":"Immunity"},{"issue":"11","key":"4431_CR16","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.3390\/cells10112962","volume":"10","author":"A Santarsiero","year":"2021","unstructured":"Santarsiero A, Convertini P, Todisco S, Pierri CL, De Grassi A, Williams NC, et al. ACLY nuclear translocation in human macrophages drives proinflammatory gene expression by NF-kappaB acetylation. Cells. 2021;10(11):2962.","journal-title":"Cells"},{"key":"4431_CR17","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2021.595371","volume":"8","author":"AP Delli Bovi","year":"2021","unstructured":"Delli Bovi AP, Marciano F, Mandato C, Siano MA, Savoia M, Vajro P. Oxidative stress in non-alcoholic fatty liver disease. An updated mini review. Front Med. 2021;8: 595371.","journal-title":"Front Med"},{"issue":"2","key":"4431_CR18","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3390\/medicina55020026","volume":"55","author":"A Ore","year":"2019","unstructured":"Ore A, Akinloye OA. Oxidative stress and antioxidant biomarkers in clinical and experimental models of non-alcoholic fatty liver disease. Medicina. 2019;55(2):26.","journal-title":"Medicina"},{"issue":"1","key":"4431_CR19","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3390\/cancers12010068","volume":"12","author":"S Todisco","year":"2019","unstructured":"Todisco S, Convertini P, Iacobazzi V, Infantino V. TCA cycle rewiring as emerging metabolic signature of hepatocellular carcinoma. Cancers. 2019;12(1):68.","journal-title":"Cancers"},{"issue":"6","key":"4431_CR20","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.cmet.2022.05.004","volume":"34","author":"MR Morrow","year":"2022","unstructured":"Morrow MR, Batchuluun B, Wu J, Ahmadi E, Leroux JM, Mohammadi-Shemirani P, et al. Inhibition of ATP-citrate lyase improves NASH, liver fibrosis, and dyslipidemia. Cell Metab. 2022;34(6):919-936.e8.","journal-title":"Cell Metab"},{"key":"4431_CR21","doi-asserted-by":"crossref","first-page":"5533793","DOI":"10.1155\/2021\/5533793","volume":"2021","author":"A Santarsiero","year":"2021","unstructured":"Santarsiero A, Convertini P, Vassallo A, Santoro V, Todisco S, Iacobazzi D, et al. Phenolic compounds of red wine Aglianico del Vulture modulate the functional activity of macrophages via inhibition of NF-kappaB and the citrate pathway. Oxid Med Cell Longev. 2021;2021:5533793.","journal-title":"Oxid Med Cell Longev"},{"issue":"7","key":"4431_CR22","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.dld.2009.08.002","volume":"42","author":"JH Lee","year":"2010","unstructured":"Lee JH, Kim D, Kim HJ, Lee CH, Yang JI, Kim W, et al. Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease. Dig Liver Dis. 2010;42(7):503\u20138.","journal-title":"Dig Liver Dis"},{"key":"4431_CR23","doi-asserted-by":"crossref","first-page":"4264815","DOI":"10.1155\/2020\/4264815","volume":"2020","author":"A Santarsiero","year":"2020","unstructured":"Santarsiero A, Onzo A, Pascale R, Acquavia MA, Coviello M, Convertini P, et al. Pistacia lentiscus hydrosol: untargeted metabolomic analysis and anti-inflammatory activity mediated by NF-kappaB and the citrate pathway. Oxid Med Cell Longev. 2020;2020:4264815.","journal-title":"Oxid Med Cell Longev"},{"key":"4431_CR24","doi-asserted-by":"crossref","first-page":"1419352","DOI":"10.1155\/2018\/1419352","volume":"2018","author":"A Santarsiero","year":"2018","unstructured":"Santarsiero A, Leccese P, Convertini P, Padula A, Abriola P, D\u2019Angelo S, et al. New Insights into Behcet\u2019s syndrome metabolic reprogramming: citrate pathway dysregulation. Mediators Inflamm. 2018;2018:1419352.","journal-title":"Mediators Inflamm"},{"issue":"4","key":"4431_CR25","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402\u20138.","journal-title":"Methods"},{"issue":"1","key":"4431_CR26","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.bbadis.2018.10.018","volume":"1865","author":"V Infantino","year":"2019","unstructured":"Infantino V, Dituri F, Convertini P, Santarsiero A, Palmieri F, Todisco S, et al. Epigenetic upregulation and functional role of the mitochondrial aspartate\/glutamate carrier isoform 1 in hepatocellular carcinoma. Biochim Biophys Acta Mol Basis Dis. 2019;1865(1):38\u201347.","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"10","key":"4431_CR27","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.3390\/nano10102080","volume":"10","author":"A Vassallo","year":"2020","unstructured":"Vassallo A, Santoro V, Pappalardo I, Santarsiero A, Convertini P, De Luca M, et al. Liposome-mediated inhibition of inflammation by hydroxycitrate. Nanomaterials. 2020;10(10):2080.","journal-title":"Nanomaterials"},{"issue":"4","key":"4431_CR28","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/imm.12659","volume":"149","author":"P Convertini","year":"2016","unstructured":"Convertini P, Menga A, Andria G, Scala I, Santarsiero A, Castiglione Morelli MA, et al. The contribution of the citrate pathway to oxidative stress in Down syndrome. Immunology. 2016;149(4):423\u201331.","journal-title":"Immunology"},{"key":"4431_CR29","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ymeth.2018.11.002","volume":"157","author":"JB Kelley","year":"2019","unstructured":"Kelley JB, Paschal BM. Fluorescence-based quantification of nucleocytoplasmic transport. Methods. 2019;157:106\u201314.","journal-title":"Methods"},{"issue":"1","key":"4431_CR30","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1055\/s-0043-118666","volume":"50","author":"S Kakino","year":"2018","unstructured":"Kakino S, Ohki T, Nakayama H, Yuan X, Otabe S, Hashinaga T, et al. Pivotal role of TNF-alpha in the development and progression of nonalcoholic fatty liver disease in a murine model. Horm Metab Res. 2018;50(1):80\u20137.","journal-title":"Horm Metab Res"},{"issue":"11","key":"4431_CR31","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.1111\/jgh.15631","volume":"36","author":"V Potoupni","year":"2021","unstructured":"Potoupni V, Georgiadou M, Chatzigriva E, Polychronidou G, Markou E, Zapantis Gakis C, et al. Circulating tumor necrosis factor-alpha levels in non-alcoholic fatty liver disease: a systematic review and a meta-analysis. J Gastroenterol Hepatol. 2021;36(11):3002\u201314.","journal-title":"J Gastroenterol Hepatol"},{"issue":"18","key":"4431_CR32","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1007\/s00018-018-2860-6","volume":"75","author":"DH Ipsen","year":"2018","unstructured":"Ipsen DH, Lykkesfeldt J, Tveden-Nyborg P. Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease. Cell Mol Life Sci. 2018;75(18):3313\u201327.","journal-title":"Cell Mol Life Sci"},{"issue":"3","key":"4431_CR33","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1002\/hep.22423","volume":"48","author":"KL Ma","year":"2008","unstructured":"Ma KL, Ruan XZ, Powis SH, Chen Y, Moorhead JF, Varghese Z. Inflammatory stress exacerbates lipid accumulation in hepatic cells and fatty livers of apolipoprotein E knockout mice. Hepatology. 2008;48(3):770\u201381.","journal-title":"Hepatology"},{"issue":"4","key":"4431_CR34","doi-asserted-by":"crossref","first-page":"G583","DOI":"10.1152\/ajpgi.00422.2005","volume":"290","author":"RF Schwabe","year":"2006","unstructured":"Schwabe RF, Brenner DA. Mechanisms of liver injury. I. TNF-alpha-induced liver injury: role of IKK, JNK, and ROS pathways. Am J Physiol Gastrointest Liver Physiol. 2006;290(4):G583\u20139.","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"3","key":"4431_CR35","first-page":"G387","volume":"275","author":"CA Bradham","year":"1998","unstructured":"Bradham CA, Plumpe J, Manns MP, Brenner DA, Trautwein C. Mechanisms of hepatic toxicity. I. TNF-induced liver injury. Am J Physiol. 1998;275(3):G387\u201392.","journal-title":"Am J Physiol"},{"issue":"1","key":"4431_CR36","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.bbrc.2013.09.037","volume":"440","author":"V Infantino","year":"2013","unstructured":"Infantino V, Iacobazzi V, Palmieri F, Menga A. ATP-citrate lyase is essential for macrophage inflammatory response. Biochem Biophys Res Commun. 2013;440(1):105\u201311.","journal-title":"Biochem Biophys Res Commun"},{"issue":"4","key":"4431_CR37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-017-0013-x","volume":"50","author":"X Dou","year":"2018","unstructured":"Dou X, Li S, Hu L, Ding L, Ma Y, Ma W, et al. Glutathione disulfide sensitizes hepatocytes to TNFalpha-mediated cytotoxicity via IKK-beta S-glutathionylation: a potential mechanism underlying non-alcoholic fatty liver disease. Exp Mol Med. 2018;50(4):1\u201316.","journal-title":"Exp Mol Med"},{"issue":"9","key":"4431_CR38","doi-asserted-by":"crossref","first-page":"4642","DOI":"10.3390\/ijms22094642","volume":"22","author":"CA Juan","year":"2021","unstructured":"Juan CA, Perez de la Lastra JM, Plou FJ, Perez-Lebena E. The chemistry of reactive oxygen species (ROS) revisited: outlining their role in biological macromolecules (DNA, lipids and proteins) and induced pathologies. Int J Mol Sci. 2021;22(9):4642.","journal-title":"Int J Mol Sci"},{"issue":"6","key":"4431_CR39","first-page":"3301","volume":"13","author":"AA Beg","year":"1993","unstructured":"Beg AA, Finco TS, Nantermet PV, Baldwin AS Jr. Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of I kappa B alpha: a mechanism for NF-kappa B activation. Mol Cell Biol. 1993;13(6):3301\u201310.","journal-title":"Mol Cell Biol"},{"key":"4431_CR40","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/1476-4598-9-117","volume":"9","author":"KT Bauerle","year":"2010","unstructured":"Bauerle KT, Schweppe RE, Haugen BR. Inhibition of nuclear factor-kappa B differentially affects thyroid cancer cell growth, apoptosis, and invasion. Mol Cancer. 2010;9:117.","journal-title":"Mol Cancer"},{"issue":"5930","key":"4431_CR41","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1126\/science.1164097","volume":"324","author":"KE Wellen","year":"2009","unstructured":"Wellen KE, Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR, Thompson CB. ATP-citrate lyase links cellular metabolism to histone acetylation. Science. 2009;324(5930):1076\u201380.","journal-title":"Science"},{"issue":"4","key":"4431_CR42","first-page":"327","volume":"16","author":"A Hadinia","year":"2019","unstructured":"Hadinia A, Doustimotlagh AH, Goodarzi HR, Arya A, Jafarinia M. Circulating levels of pro-inflammatory cytokines in patients with nonalcoholic fatty liver disease and non-alcoholic steatohepatitis. Iran J Immunol. 2019;16(4):327\u201333.","journal-title":"Iran J Immunol"},{"key":"4431_CR43","volume":"13","author":"Y Duan","year":"2022","unstructured":"Duan Y, Pan X, Luo J, Xiao X, Li J, Bestman PL, et al. Association of inflammatory cytokines with non-alcoholic fatty liver disease. Front Immunol. 2022;13: 880298.","journal-title":"Front Immunol"},{"issue":"3","key":"4431_CR44","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1158\/1078-0432.CCR-21-1258","volume":"29","author":"M Pinter","year":"2023","unstructured":"Pinter M, Pinato DJ, Ramadori P, Heikenwalder M. NASH and hepatocellular carcinoma: immunology and immunotherapy. Clin Cancer Res. 2023;29(3):513\u201320.","journal-title":"Clin Cancer Res"},{"key":"4431_CR45","volume":"127","author":"Z Liu","year":"2022","unstructured":"Liu Z, Lin C, Suo C, Zhao R, Jin L, Zhang T, et al. Metabolic dysfunction-associated fatty liver disease and the risk of 24 specific cancers. Metabolism. 2022;127: 154955.","journal-title":"Metabolism"},{"issue":"2","key":"4431_CR46","doi-asserted-by":"crossref","first-page":"168","DOI":"10.5009\/gnl19069","volume":"14","author":"AA Li","year":"2020","unstructured":"Li AA, Ahmed A, Kim D. Extrahepatic manifestations of nonalcoholic fatty liver disease. Gut Liver. 2020;14(2):168\u201378.","journal-title":"Gut Liver"},{"key":"4431_CR47","doi-asserted-by":"publisher","DOI":"10.1007\/s13679-023-00519-y","author":"ID Vachliotis","year":"2023","unstructured":"Vachliotis ID, Polyzos SA. The role of tumor necrosis factor-alpha in the pathogenesis and treatment of nonalcoholic fatty liver disease. Curr Obes Rep. 2023. https:\/\/doi.org\/10.1007\/s13679-023-00519-y.","journal-title":"Curr Obes Rep"},{"issue":"1","key":"4431_CR48","doi-asserted-by":"crossref","first-page":"6296","DOI":"10.1038\/s41467-020-20141-z","volume":"11","author":"J Baardman","year":"2020","unstructured":"Baardman J, Verberk SGS, van der Velden S, Gijbels MJJ, van Roomen C, Sluimer JC, et al. Macrophage ATP citrate lyase deficiency stabilizes atherosclerotic plaques. Nat Commun. 2020;11(1):6296.","journal-title":"Nat Commun"},{"issue":"1","key":"4431_CR49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11154-013-9271-7","volume":"15","author":"M Matsuda","year":"2014","unstructured":"Matsuda M, Shimomura I. Roles of adiponectin and oxidative stress in obesity-associated metabolic and cardiovascular diseases. Rev Endocr Metab Disord. 2014;15(1):1\u201310.","journal-title":"Rev Endocr Metab Disord"},{"key":"4431_CR50","doi-asserted-by":"crossref","first-page":"7580707","DOI":"10.1155\/2018\/7580707","volume":"2018","author":"L Li","year":"2018","unstructured":"Li L, Yang X. The essential element manganese, oxidative stress, and metabolic diseases: links and interactions. Oxid Med Cell Longev. 2018;2018:7580707.","journal-title":"Oxid Med Cell Longev"},{"issue":"7","key":"4431_CR51","doi-asserted-by":"crossref","first-page":"e180","DOI":"10.1111\/liv.12523","volume":"34","author":"Z Tariq","year":"2014","unstructured":"Tariq Z, Green CJ, Hodson L. Are oxidative stress mechanisms the common denominator in the progression from hepatic steatosis towards non-alcoholic steatohepatitis (NASH)? Liver Int. 2014;34(7):e180\u201390.","journal-title":"Liver Int"},{"key":"4431_CR52","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.freeradbiomed.2020.02.025","volume":"152","author":"Z Chen","year":"2020","unstructured":"Chen Z, Tian R, She Z, Cai J, Li H. Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease. Free Radic Biol Med. 2020;152:116\u201341.","journal-title":"Free Radic Biol Med"},{"issue":"6","key":"4431_CR53","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1083\/jcb.201708007","volume":"217","author":"Y Wang","year":"2018","unstructured":"Wang Y, Branicky R, Noe A, Hekimi S. Superoxide dismutases: dual roles in controlling ROS damage and regulating ROS signaling. J Cell Biol. 2018;217(6):1915\u201328.","journal-title":"J Cell Biol"},{"issue":"3","key":"4431_CR54","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/s41575-018-0082-x","volume":"16","author":"K Kazankov","year":"2019","unstructured":"Kazankov K, Jorgensen SMD, Thomsen KL, Moller HJ, Vilstrup H, George J, et al. The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Nat Rev Gastroenterol Hepatol. 2019;16(3):145\u201359.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"4","key":"4431_CR55","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.jhep.2018.11.034","volume":"70","author":"S de Oliveira","year":"2019","unstructured":"de Oliveira S, Houseright RA, Graves AL, Golenberg N, Korte BG, Miskolci V, et al. Metformin modulates innate immune-mediated inflammation and early progression of NAFLD-associated hepatocellular carcinoma in zebrafish. J Hepatol. 2019;70(4):710\u201321.","journal-title":"J Hepatol"},{"issue":"11","key":"4431_CR56","doi-asserted-by":"crossref","first-page":"3024","DOI":"10.1111\/febs.15877","volume":"289","author":"R Thibaut","year":"2022","unstructured":"Thibaut R, Gage MC, Pineda-Torra I, Chabrier G, Venteclef N, Alzaid F. Liver macrophages and inflammation in physiology and physiopathology of non-alcoholic fatty liver disease. FEBS J. 2022;289(11):3024\u201357.","journal-title":"FEBS J"},{"issue":"4","key":"4431_CR57","doi-asserted-by":"crossref","DOI":"10.1002\/edm2.194","volume":"3","author":"MV Chakravarthy","year":"2020","unstructured":"Chakravarthy MV, Neuschwander-Tetri BA. The metabolic basis of nonalcoholic steatohepatitis. Endocrinol Diabetes Metab. 2020;3(4): e00112.","journal-title":"Endocrinol Diabetes Metab"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-023-04431-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-023-04431-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-023-04431-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T16:46:28Z","timestamp":1729961188000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/s12967-023-04431-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,24]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["4431"],"URL":"https:\/\/doi.org\/10.1186\/s12967-023-04431-w","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,24]]},"assertion":[{"value":"8 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 August 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was carried out in accordance with the Declaration of Helsinki and in agreement with local Italian Committee on Human Research\u2019s approved procedures (REF. TS\/CEUR 20200034750\u201415 September 2020). All subjects provided written, informed consent, authorizing the use of their material for this research activity.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors agree to the publication of the article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"568"}}