{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:44:08Z","timestamp":1790775848030,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III","award":["PI15\/00285"],"award-info":[{"award-number":["PI15\/00285"]}]},{"name":"Instituto de Salud Carlos III","award":["PI18\/00921"],"award-info":[{"award-number":["PI18\/00921"]}]},{"name":"Instituto de Salud Carlos III","award":["PI18\/01590"],"award-info":[{"award-number":["PI18\/01590"]}]},{"name":"Instituto de Salud Carlos III","award":["CPII\/00023"],"award-info":[{"award-number":["CPII\/00023"]}]},{"name":"Instituto de Salud Carlos III","award":["SGR1227"],"award-info":[{"award-number":["SGR1227"]}]},{"name":"Instituto de Salud Carlos III","award":["60\/U\/2016"],"award-info":[{"award-number":["60\/U\/2016"]}]},{"name":"Instituto de Salud Carlos III","award":["PGC2018-096244-B-I00"],"award-info":[{"award-number":["PGC2018-096244-B-I00"]}]},{"DOI":"10.13039\/501100002809","name":"European Regional Development Fund [FEDER], the Generalitat de Catalunya, Barcelona, Spain","doi-asserted-by":"publisher","award":["PI15\/00285"],"award-info":[{"award-number":["PI15\/00285"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"European Regional Development Fund [FEDER], the Generalitat de Catalunya, Barcelona, Spain","doi-asserted-by":"publisher","award":["PI18\/00921"],"award-info":[{"award-number":["PI18\/00921"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"European Regional Development Fund [FEDER], the Generalitat de Catalunya, Barcelona, Spain","doi-asserted-by":"publisher","award":["PI18\/01590"],"award-info":[{"award-number":["PI18\/01590"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"European Regional Development Fund [FEDER], the Generalitat de Catalunya, Barcelona, Spain","doi-asserted-by":"publisher","award":["CPII\/00023"],"award-info":[{"award-number":["CPII\/00023"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"European Regional Development Fund [FEDER], the Generalitat de Catalunya, Barcelona, Spain","doi-asserted-by":"publisher","award":["SGR1227"],"award-info":[{"award-number":["SGR1227"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"European Regional Development Fund [FEDER], the Generalitat de Catalunya, Barcelona, Spain","doi-asserted-by":"publisher","award":["60\/U\/2016"],"award-info":[{"award-number":["60\/U\/2016"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"European Regional Development Fund [FEDER], the Generalitat de Catalunya, Barcelona, Spain","doi-asserted-by":"publisher","award":["PGC2018-096244-B-I00"],"award-info":[{"award-number":["PGC2018-096244-B-I00"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 La Marat\u00f3 de TV3","doi-asserted-by":"publisher","award":["PI15\/00285"],"award-info":[{"award-number":["PI15\/00285"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 La Marat\u00f3 de TV3","doi-asserted-by":"publisher","award":["PI18\/00921"],"award-info":[{"award-number":["PI18\/00921"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 La Marat\u00f3 de TV3","doi-asserted-by":"publisher","award":["PI18\/01590"],"award-info":[{"award-number":["PI18\/01590"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 La Marat\u00f3 de TV3","doi-asserted-by":"publisher","award":["CPII\/00023"],"award-info":[{"award-number":["CPII\/00023"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 La Marat\u00f3 de TV3","doi-asserted-by":"publisher","award":["SGR1227"],"award-info":[{"award-number":["SGR1227"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 La Marat\u00f3 de TV3","doi-asserted-by":"publisher","award":["60\/U\/2016"],"award-info":[{"award-number":["60\/U\/2016"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 La Marat\u00f3 de TV3","doi-asserted-by":"publisher","award":["PGC2018-096244-B-I00"],"award-info":[{"award-number":["PGC2018-096244-B-I00"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Science, Innovation and Universities, Madrid, Spain","award":["PI15\/00285"],"award-info":[{"award-number":["PI15\/00285"]}]},{"name":"Ministry of Science, Innovation and Universities, Madrid, Spain","award":["PI18\/00921"],"award-info":[{"award-number":["PI18\/00921"]}]},{"name":"Ministry of Science, Innovation and Universities, Madrid, Spain","award":["PI18\/01590"],"award-info":[{"award-number":["PI18\/01590"]}]},{"name":"Ministry of Science, Innovation and Universities, Madrid, Spain","award":["CPII\/00023"],"award-info":[{"award-number":["CPII\/00023"]}]},{"name":"Ministry of Science, Innovation and Universities, Madrid, Spain","award":["SGR1227"],"award-info":[{"award-number":["SGR1227"]}]},{"name":"Ministry of Science, Innovation and Universities, Madrid, Spain","award":["60\/U\/2016"],"award-info":[{"award-number":["60\/U\/2016"]}]},{"name":"Ministry of Science, Innovation and Universities, Madrid, Spain","award":["PGC2018-096244-B-I00"],"award-info":[{"award-number":["PGC2018-096244-B-I00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The surgically induced remission of liver disease represents a model to investigate the signalling processes that trigger the development of nonalcoholic steatohepatitis with the aim of identifying novel therapeutic targets. We recruited patients with severe obesity with or without nonalcoholic steatohepatitis and obtained liver and plasma samples before and after laparoscopic sleeve gastrectomy for immunoblotting, immunocytochemical, metabolomic, transcriptomic and epigenetic analyses. Functional studies were performed in HepG2 cells and primary hepatocytes. Surgery was associated with a decrease in the inflammatory response and revealed the role of mitogen-activated protein kinases. Nonalcoholic steatohepatitis was associated with an increased glutaminolysis-induced production of \u03b1-ketoglutarate and the hyperactivation of mammalian target of rapamycin complex 1. These changes were crucial for adenosine monophosphate-activated protein kinase\/mammalian target of rapamycin-driven pathways that modulated hepatocyte survival by coordinating apoptosis and autophagy and affected methylation-related epigenomic remodelling enzymes. Hepatic transcriptome signatures and differentially methylated genomic regions distinguished patients with and without steatohepatitis. Our results suggest that the increased glutaminolysis-induced \u03b1-ketoglutarate production and the mammalian target of rapamycin complex 1 dysregulation play a crucial role in the inefficient adaptive responses leading to steatohepatitis in obesity.<\/jats:p>","DOI":"10.3390\/ijms23147830","type":"journal-article","created":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T22:57:06Z","timestamp":1658098626000},"page":"7830","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Laparoscopic Sleeve Gastrectomy in Patients with Severe Obesity Restores Adaptive Responses Leading to Nonalcoholic Steatohepatitis"],"prefix":"10.3390","volume":"23","author":[{"given":"Noem\u00ed","family":"Cabr\u00e9","sequence":"first","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Department of Surgery, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Vigili, 43204 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fedra","family":"Luciano-Mateo","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Department of Surgery, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Vigili, 43204 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6730-7627","authenticated-orcid":false,"given":"Douglas J.","family":"Chapski","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Baiges-Gaya","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Department of Surgery, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Vigili, 43204 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvador","family":"Fern\u00e1ndez-Arroyo","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Department of Surgery, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Vigili, 43204 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0954-295X","authenticated-orcid":false,"given":"Anna","family":"Hern\u00e1ndez-Aguilera","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Department of Surgery, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Vigili, 43204 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Casta\u00f1\u00e9","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Department of Surgery, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Vigili, 43204 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Rodr\u00edguez-Tom\u00e0s","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Department of Surgery, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Vigili, 43204 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Par\u00eds","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Department of Surgery, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Vigili, 43204 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e0tima","family":"Sabench","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Department of Surgery, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Vigili, 43204 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Del","family":"Castillo","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Department of Surgery, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Vigili, 43204 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0700-2004","authenticated-orcid":false,"given":"Josep M.","family":"del Bas","sequence":"additional","affiliation":[{"name":"Technological Unit of Nutrition and Health, EURECAT Technology Center of Catalonia, 43204 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Tom\u00e9","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda Molecular y Medicina Regenerativa, CSIC, University of Sevilla, 41004 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0532-8852","authenticated-orcid":false,"given":"Cl\u00e9ment","family":"Bodineau","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda Molecular y Medicina Regenerativa, CSIC, University of Sevilla, 41004 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Sola-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda Molecular y Medicina Regenerativa, CSIC, University of Sevilla, 41004 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8844-0718","authenticated-orcid":false,"given":"Jos\u00e9","family":"L\u00f3pez-Miranda","sequence":"additional","affiliation":[{"name":"Lipids and Atherosclerosis Unit, IMIBIC\/Reina Sof\u00eda University Hospital, CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, ISCIII, 28029 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3886-5355","authenticated-orcid":false,"given":"Alejandro","family":"Mart\u00edn-Montalvo","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda Molecular y Medicina Regenerativa, CSIC, University of Sevilla, 41004 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal V.","family":"Dur\u00e1n","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda Molecular y Medicina Regenerativa, CSIC, University of Sevilla, 41004 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Vondriska","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2169-3972","authenticated-orcid":false,"given":"Manuel","family":"Rosa-Garrido","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Alabama, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3165-3640","authenticated-orcid":false,"given":"Jordi","family":"Camps","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Department of Surgery, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Vigili, 43204 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8733-4561","authenticated-orcid":false,"given":"Javier A.","family":"Men\u00e9ndez","sequence":"additional","affiliation":[{"name":"Girona Biomedical Center and Program against Cancer Therapeutic Resistance, Catalan Institute of Oncology, 08908 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2749-4541","authenticated-orcid":false,"given":"Jorge","family":"Joven","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Department of Surgery, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Hospital Universitari de Sant Joan, Universitat Rovira i Vigili, 43204 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.metabol.2018.11.014","article-title":"Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics","volume":"92","author":"Polyzos","year":"2019","journal-title":"Metabolism"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.cmet.2015.04.004","article-title":"Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis","volume":"21","author":"Koliaki","year":"2015","journal-title":"Cell. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.cell.2019.04.010","article-title":"Deficient endoplasmic reticulum-mitochondrial phosphatidylserine transfer causes liver disease","volume":"177","author":"Vives","year":"2019","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/978-1-4939-0888-2_7","article-title":"Cell cycle regulation by the nutrient-sensing mammalian target of rapamycin (mTOR) pathway","volume":"1170","author":"Joven","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7529","DOI":"10.3748\/wjg.v21.i24.7529","article-title":"Liver fat deposition and mitochondrial dysfunction in morbid obesity: An approach combining metabolomics with liver imaging and histology","volume":"21","author":"Calvo","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1111\/apt.15606","article-title":"Plasma metabolic alterations in patients with severe obesity and non-alcoholic steatohepatitis","volume":"51","author":"Sabench","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1007\/s13361-015-1262-3","article-title":"Exploring the process of energy generation in pathophysiology by trgeted metabolomics: Performance of a simple and quantitative method","volume":"27","author":"Luciano","year":"2016","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1053\/j.gastro.2018.06.083","article-title":"Mitochondrial dysfunction and signaling in chronic liver diseases","volume":"155","author":"Mansouri","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/nrc.2016.85","article-title":"Altered metabolite levels in cancer: Implications for tumour biology and cancer therapy","volume":"16","author":"Sullivan","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.jhep.2017.09.003","article-title":"Genetics and epigenetics of NAFLD and NASH: Clinical impact","volume":"68","author":"Eslam","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1128\/MCB.01338-07","article-title":"Loss of the SdhB, but Not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis","volume":"28","author":"Guzy","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1080\/15548627.2017.1299315","article-title":"Glutamoptosis: A new cell death mechanism inhibited by autophagy during nutritional imbalance","volume":"13","author":"Villar","year":"2017","journal-title":"Autophagy"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"348","DOI":"10.18632\/aging.100316","article-title":"Gerosuppressant metformin: Less is more","volume":"3","author":"Menendez","year":"2011","journal-title":"Aging"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1038\/ncb2324","article-title":"NF-\u03baB controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration","volume":"13","author":"Mauro","year":"2011","journal-title":"Nat. Cell. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.molcel.2016.02.022","article-title":"Mitofusins, from mitochondria to metabolism","volume":"61","author":"Schrepfer","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.metabol.2019.07.002","article-title":"Laparoscopic sleeve gastrectomy reverses non-alcoholic fatty liver disease modulating oxidative stress and inflammation","volume":"99","author":"Fibla","year":"2019","journal-title":"Metabolism"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1111\/apt.16262","article-title":"Cross-linkage between bacterial taxonomy and gene functions: A study of metagenome-assembled genomes of gut microbiota in adult non-alcoholic fatty liver disease","volume":"53","author":"Canivet","year":"2021","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/hep4.1479","article-title":"Pathogenesis of nonalcoholic steatohepatitis: An overview","volume":"4","author":"Parthasarathy","year":"2020","journal-title":"Hepatol. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1053\/j.gastro.2014.07.018","article-title":"Cell death and cell death responses in liver disease: Mechanisms and clinical relevance","volume":"147","author":"Luedde","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/ijo.2014.53","article-title":"Mapping of the circulating metabolome reveals \u03b1-ketoglutarate as a predictor of morbid obesity-associated non-alcoholic fatty liver disease","volume":"39","author":"Guirro","year":"2015","journal-title":"Int. J. Obes."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.jhep.2019.12.015","article-title":"OGDHL silencing promotes hepatocellular carcinoma by reprogramming glutamine metabolism","volume":"72","author":"Dai","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.cmet.2020.01.013","article-title":"Targeting hepatic glutaminase 1 ameliorates non-alcoholic steatohepatitis by restoring very-low-density lipoprotein triglyceride assembly","volume":"31","author":"Simon","year":"2020","journal-title":"Cell. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/nature13981","article-title":"Intracellular \u03b1-ketoglutarate maintains the pluripotency of embryonic stem cells","volume":"518","author":"Carey","year":"2015","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.jhep.2011.09.020","article-title":"Obesity, inflammation, and liver cancer","volume":"56","author":"Sun","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1126\/science.aay0542","article-title":"An AMPK-caspase-6 axis controls liver damage in nonalcoholic steatohepatitis","volume":"367","author":"Zhao","year":"2020","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.cgh.2020.04.083","article-title":"Type 2 diabetes and metformin use associate with outcomes of patients with nonalcoholic steatohepatitis-related, Child-Pugh A cirrhosis","volume":"19","author":"Wong","year":"2021","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.cmet.2013.07.004","article-title":"DNA methylation analysis in nonalcoholic fatty liver disease suggests distinct disease-specific and remodeling signatures after bariatric surgery","volume":"18","author":"Ahrens","year":"2013","journal-title":"Cell. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"G462","DOI":"10.1152\/ajpgi.00358.2018","article-title":"Hepatic transcriptome signatures in patients with varying degrees of nonalcoholic fatty liver disease compared with healthy normal-weight individuals","volume":"316","author":"Suppli","year":"2019","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1002\/hep.25762","article-title":"The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association","volume":"55","author":"Chalasani","year":"2012","journal-title":"Hepatology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic atty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref_31","first-page":"953841","article-title":"Ubiquitous transgenic overexpression of C-C chemokine ligand 2: A model to assess the combined effect of high energy intake and continuous low-grade inflammation","volume":"2013","author":"Rull","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1016\/j.bbadis.2019.03.006","article-title":"Chemokine (C-C motif) ligand 2 gene ablation protects low-density lipoprotein and paraoxonase-1 double deficient mice from liver injury, oxidative stress and inflammation","volume":"1865","author":"Menendez","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/onc.2017.367","article-title":"Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism","volume":"37","author":"Verdura","year":"2018","journal-title":"Oncogene"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1093\/bioinformatics\/btu775","article-title":"Genomation: A toolkit to summarize, annotate and visualize genomic intervals","volume":"31","author":"Akalin","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1093\/bioinformatics\/btu393","article-title":"Circlize implements and enhances circular visualization in R","volume":"30","author":"Gu","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1161\/CIRCULATIONAHA.117.029430","article-title":"High-resolution mapping of chromatin conformation in cardiac myocytes reveals structural remodeling of the epigenome in heart failure","volume":"136","author":"Chapski","year":"2017","journal-title":"Circulation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s00277-010-0901-9","article-title":"Effects of C282Y, H63D, and S65C HFE gene mutations, diet, and life-style factors on iron status in a general Mediterranean population from Tarragona, Spain","volume":"89","author":"Aranda","year":"2010","journal-title":"Ann. Hematol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.soard.2019.10.025","article-title":"Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures","volume":"16","author":"Mechanick","year":"2020","journal-title":"Surg. Obes. Relat. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1007\/s11695-017-2700-z","article-title":"Analysis of gastric physiology after laparoscopic sleeve gastrectomy (LSG) with or without antral preservation in relation to metabolic response: \tA randomised study","volume":"27","author":"Vives","year":"2017","journal-title":"Obes. Surg."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhang, W., Sargis, R.M., Volden, P.A., Carmean, C.M., Sun, X.J., and Brady, M.J. (2012). PCB 126 and other dioxin-like PCBs specifically suppress hepatic PEPCK expression via the aryl hydrocarbon receptor. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037103"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1083\/jcb.201607091","article-title":"The transcriptional regulator of the chaperone response HSF1 controls hepatic bioenergetics and protein homeostasis","volume":"216","author":"Qiao","year":"2017","journal-title":"J. Cell Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/14\/7830\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:51:35Z","timestamp":1760140295000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/14\/7830"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,15]]},"references-count":41,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijms23147830"],"URL":"https:\/\/doi.org\/10.3390\/ijms23147830","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,15]]}}}