{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T02:25:47Z","timestamp":1779416747584,"version":"3.53.1"},"reference-count":49,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003107","name":"German Federal Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003107","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["101170408"],"award-info":[{"award-number":["101170408"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Forschung, Technologie und Raumfahrt","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014690","name":"Ministry of Culture and Science of the State of North Rhine-Westphalia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014690","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jhep-reports.eu","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["JHEP Reports"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1016\/j.jhepr.2026.101792","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T16:44:05Z","timestamp":1771605845000},"page":"101792","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["A thioacrylamide-based compound directly counteracts hepatic fibrosis with profound anti-obesity action"],"prefix":"10.1016","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5950-9619","authenticated-orcid":false,"given":"Elisabeth","family":"Rohbeck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0622-6928","authenticated-orcid":false,"given":"Corinna","family":"Niersmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bedair","family":"Dewidar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"K\u00f6hrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Wachtmeister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8856-5799","authenticated-orcid":false,"given":"Bruno","family":"Guigas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1140-6204","authenticated-orcid":false,"given":"Volker M.","family":"Lauschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Margriet","family":"Ouwens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8200-6382","authenticated-orcid":false,"given":"Michael","family":"Roden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Eckel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jhepr.2026.101792_bib1","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1056\/NEJMra1503519","article-title":"Cause, Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis","volume":"377","author":"Diehl","year":"2017","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jhepr.2026.101792_bib2","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/nrgastro.2013.171","article-title":"The global NAFLD epidemic","volume":"10","author":"Loomba","year":"2013","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.jhepr.2026.101792_bib3","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1053\/j.gastro.2020.01.052","article-title":"Nonalcoholic Fatty Liver Disease 2020: The State of the Disease","volume":"158","author":"Cotter","year":"2020","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jhepr.2026.101792_bib4","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/164_2021_561","article-title":"NAFLD and NASH: The Metabolically Diseased Liver","volume":"274","author":"Armandi","year":"2022","journal-title":"Handb Exp Pharmacol"},{"key":"10.1016\/j.jhepr.2026.101792_bib5","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1053\/j.gastro.2008.03.003","article-title":"Mechanisms of Hepatic Fibrogenesis","volume":"134","author":"Friedman","year":"2008","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jhepr.2026.101792_bib6","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrgastro.2017.38","article-title":"Mechanisms of hepatic stellate cell activation","volume":"14","author":"Tsuchida","year":"2017","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.jhepr.2026.101792_bib7","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2020.104720","article-title":"Intercellular crosstalk of hepatic stellate cells in liver fibrosis: New insights into therapy","volume":"155","author":"Cai","year":"2020","journal-title":"Pharmacol Res"},{"key":"10.1016\/j.jhepr.2026.101792_bib8","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/s41587-023-01787-8","article-title":"NASH therapies head toward landmark approval","volume":"41","author":"Dolgin","year":"2023","journal-title":"Nat Biotechnol"},{"key":"10.1016\/j.jhepr.2026.101792_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2025.108811","article-title":"Insights into the results of Resmetirom trials: Can a thyroid hormone receptor agonist be the holy grail of MASH therapy?","volume":"268","author":"Arvanitakis","year":"2025","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.jhepr.2026.101792_bib10","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.jhep.2023.03.038","article-title":"An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH","volume":"79","author":"Tacke","year":"2023","journal-title":"J Hepatol"},{"key":"10.1016\/j.jhepr.2026.101792_bib11","article-title":"Antifibrotic therapies for metabolic dysfunction-associated steatotic liver disease","volume":"7","author":"Schwabe","year":"2025","journal-title":"JHEP Rep"},{"key":"10.1016\/j.jhepr.2026.101792_bib12","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1111\/dom.14719","article-title":"Positive allosteric \u03b3-aminobutyric acid type A receptor modulation prevents lipotoxicity-induced injury in hepatocytes in vitro","volume":"24","author":"Rohbeck","year":"2022","journal-title":"Diabetes Obes Metab"},{"key":"10.1016\/j.jhepr.2026.101792_bib13","article-title":"Insulin-dependent glucose consumption dynamics in 3D primary human liver cultures measured by a sensitive and specific glucose sensor with nanoliter input volume","volume":"35","author":"Kemas","year":"2021","journal-title":"FASEB J Off Publ Fed Am Soc Exp Biol"},{"key":"10.1016\/j.jhepr.2026.101792_bib14","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0213650","article-title":"Sfrp5 increases glucose-stimulated insulin secretion in the rat pancreatic beta cell line INS-1E","volume":"14","author":"Carstensen-Kirberg","year":"2019","journal-title":"PloS One"},{"key":"10.1016\/j.jhepr.2026.101792_bib15","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1159\/000506405","article-title":"Increased Release of Proinflammatory Proteins in Primary Human Adipocytes and Activation of the Inflammatory NFKB, p38, and ERK Pathways upon Omentin Treatment","volume":"13","author":"Niersmann","year":"2020","journal-title":"Obes Facts"},{"key":"10.1016\/j.jhepr.2026.101792_bib16","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2023.1106075","article-title":"Positive allosteric GABAA receptor modulation counteracts lipotoxicity-induced gene expression changes in hepatocytes in vitro","volume":"14","author":"Rohbeck","year":"2023","journal-title":"Front Physiol"},{"key":"10.1016\/j.jhepr.2026.101792_bib17","doi-asserted-by":"crossref","first-page":"4019","DOI":"10.1093\/hmg\/ddac150","article-title":"Comparative genomic analyses of multiple backcross mouse populations suggest SGCG as a novel potential obesity-modifier gene","volume":"31","author":"Kuhn","year":"2022","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.jhepr.2026.101792_bib18","doi-asserted-by":"crossref","DOI":"10.15252\/embr.202256380","article-title":"Calculation of ATP production rates using the Seahorse XF Analyzer","volume":"24","author":"Desousa","year":"2023","journal-title":"EMBO Rep"},{"key":"10.1016\/j.jhepr.2026.101792_bib19","article-title":"Nudix hydrolase NUDT19 regulates mitochondrial function and ATP production in murine hepatocytes","volume":"1867","author":"G\u00f6rigk","year":"2022","journal-title":"Biochim Biophys Acta BBA - Mol Cell Biol Lipids"},{"key":"10.1016\/j.jhepr.2026.101792_bib20","doi-asserted-by":"crossref","first-page":"7056","DOI":"10.1038\/s41467-021-27153-3","article-title":"High-intensity training induces non-stoichiometric changes in the mitochondrial proteome of human skeletal muscle without reorganisation of respiratory chain content","volume":"12","author":"Granata","year":"2021","journal-title":"Nat Commun"},{"key":"10.1016\/j.jhepr.2026.101792_bib21","first-page":"25","article-title":"High-Resolution Respirometry: OXPHOS Protocols for Human Cells and Permeabilized Fibers from Small Biopsies of Human Muscle","volume":"810","author":"Pesta","year":"2012"},{"key":"10.1016\/j.jhepr.2026.101792_bib22","article-title":"Chemogenomic Screening in a Patient-Derived 3D Fatty Liver Disease Model Reveals the CHRM1-TRPM8 Axis as a Novel Module for Targeted Intervention","volume":"12","author":"Youhanna","year":"2025","journal-title":"Adv Sci Weinh Baden-Wurtt Ger"},{"key":"10.1016\/j.jhepr.2026.101792_bib23","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1124\/pharmrev.120.000238","article-title":"Organotypic and Microphysiological Human Tissue Models for Drug Discovery and Development-Current State-of-the-Art and Future Perspectives","volume":"74","author":"Youhanna","year":"2022","journal-title":"Pharmacol Rev"},{"key":"10.1016\/j.jhepr.2026.101792_bib24","doi-asserted-by":"crossref","DOI":"10.1172\/JCI175824","article-title":"FDA Modernization Act 2.0: transitioning beyond animal models with human cells, organoids, and AI\/ML-based approaches","volume":"133","author":"Zushin","year":"2023","journal-title":"J Clin Invest"},{"issue":"11","key":"10.1016\/j.jhepr.2026.101792_bib25","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.3390\/cells8111419","article-title":"TGF-\u03b2 in Hepatic Stellate Cell Activation and Liver Fibrogenesis","volume":"8","author":"Dewidar","year":"2019","journal-title":"Cells"},{"key":"10.1016\/j.jhepr.2026.101792_bib26","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1152\/physrev.00013.2007","article-title":"Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver","volume":"88","author":"Friedman","year":"2008","journal-title":"Physiol Rev"},{"key":"10.1016\/j.jhepr.2026.101792_bib27","doi-asserted-by":"crossref","first-page":"2917","DOI":"10.1038\/s41401-022-00907-5","article-title":"Hepatocyte-derived VEGFA accelerates the progression of non-alcoholic fatty liver disease to hepatocellular carcinoma via activating hepatic stellate cells","volume":"43","author":"Shen","year":"2022","journal-title":"Acta Pharmacol Sin"},{"key":"10.1016\/j.jhepr.2026.101792_bib28","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1476-5926-3-10","article-title":"Expression of leukemia inhibitory factor (LIF) and its receptor gp190 in human liver and in cultured human liver myofibroblasts. Cloning of new isoforms of LIF mRNA","volume":"3","author":"Hisaka","year":"2004","journal-title":"Comp Hepatol"},{"key":"10.1016\/j.jhepr.2026.101792_bib29","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/j.1365-2249.1994.tb07031.x","article-title":"IL-6 induces hepatic inflammation and collagen synthesis in vivo","volume":"95","author":"Choi","year":"1994","journal-title":"Clin Exp Immunol"},{"key":"10.1016\/j.jhepr.2026.101792_bib30","doi-asserted-by":"crossref","first-page":"7677","DOI":"10.1007\/s11033-021-06774-3","article-title":"RNA sequencing of LX-2 cells treated with TGF-\u03b21 identifies genes associated with hepatic stellate cell activation","volume":"48","author":"Carson","year":"2021","journal-title":"Mol Biol Rep"},{"key":"10.1016\/j.jhepr.2026.101792_bib31","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.omtn.2017.04.014","article-title":"Identification of Novel Fibrosis Modifiers by In Vivo siRNA Silencing","volume":"7","author":"Vollmann","year":"2017","journal-title":"Mol Ther Nucleic Acids"},{"key":"10.1016\/j.jhepr.2026.101792_bib32","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/wrr.12392","article-title":"Master regulators in primary skin fibroblast fate reprogramming in a human ex vivo model of chronic wounds","volume":"24","author":"Noizet","year":"2016","journal-title":"Wound Repair Regen"},{"key":"10.1016\/j.jhepr.2026.101792_bib33","doi-asserted-by":"crossref","first-page":"357","DOI":"10.3389\/fonc.2018.00357","article-title":"Transforming Growth Factor-\u03b2-Induced Cell Plasticity in Liver Fibrosis and Hepatocarcinogenesis","volume":"8","author":"Fabregat","year":"2018","journal-title":"Front Oncol"},{"key":"10.1016\/j.jhepr.2026.101792_bib34","doi-asserted-by":"crossref","first-page":"4107","DOI":"10.2147\/DDDT.S186726","article-title":"Ferulic acid attenuates liver fibrosis and hepatic stellate cell activation via inhibition of TGF-\u03b2\/Smad signaling pathway","volume":"12","author":"Mu","year":"2018","journal-title":"Drug Des Devel Ther"},{"key":"10.1016\/j.jhepr.2026.101792_bib35","article-title":"Physalin D attenuates hepatic stellate cell activation and liver fibrosis by blocking TGF-\u03b2\/Smad and YAP signaling","volume":"78","author":"Xiang","year":"2020","journal-title":"Phytomedicine Int J Phytother Phytopharm"},{"key":"10.1016\/j.jhepr.2026.101792_bib36","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/j.jhep.2011.07.010","article-title":"A role for autophagy during hepatic stellate cell activation","volume":"55","author":"Thoen","year":"2011","journal-title":"J Hepatol"},{"key":"10.1016\/j.jhepr.2026.101792_bib37","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1080\/15548627.2015.1058473","article-title":"Macrophage autophagy protects against liver fibrosis in mice","volume":"11","author":"Lodder","year":"2015","journal-title":"Autophagy"},{"key":"10.1016\/j.jhepr.2026.101792_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbadis.2021.166085","article-title":"The role of the retinoid receptor, RAR\/RXR heterodimer, in liver physiology","volume":"1867","author":"Li","year":"2021","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"10.1016\/j.jhepr.2026.101792_bib39","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1172\/JCI1018","article-title":"Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors","volume":"102","author":"Iredale","year":"1998","journal-title":"J Clin Invest"},{"key":"10.1016\/j.jhepr.2026.101792_bib40","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1080\/15384101.2016.1152435","article-title":"Common pathway signature in lung and liver fibrosis","volume":"15","author":"Makarev","year":"2016","journal-title":"Cell Cycle Georget Tex"},{"key":"10.1016\/j.jhepr.2026.101792_bib41","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/s41586-021-03549-5","article-title":"Cross-tissue organization of the fibroblast lineage","volume":"593","author":"Buechler","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.jhepr.2026.101792_bib42","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1006\/taap.2001.9304","article-title":"The role of tumor necrosis factor-alpha in liver toxicity, inflammation, and fibrosis induced by carbon tetrachloride","volume":"177","author":"Simeonova","year":"2001","journal-title":"Toxicol Appl Pharmacol"},{"issue":"10","key":"10.1016\/j.jhepr.2026.101792_bib43","doi-asserted-by":"crossref","DOI":"10.1097\/HC9.0000000000000254","article-title":"Serum levels of fibrogenesis biomarkers reveal distinct endotypes predictive of response to weight loss in advanced nonalcoholic fatty liver disease","volume":"7","author":"Karsdal","year":"2023","journal-title":"Hepatol Commun"},{"key":"10.1016\/j.jhepr.2026.101792_bib44","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/nrgastro.2016.147","article-title":"NAFLD and diabetes mellitus","volume":"14","author":"Tilg","year":"2017","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.jhepr.2026.101792_bib45","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1053\/j.gastro.2007.03.054","article-title":"Biology of Incretins: GLP-1 and GIP","volume":"132","author":"Baggio","year":"2007","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jhepr.2026.101792_bib46","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/dom.15728","article-title":"Changes in lean body mass with glucagon-like peptide -1-based therapies and mitigation strategies","volume":"26","author":"Neeland","year":"2024","journal-title":"Diabetes Obes Metab"},{"key":"10.1016\/j.jhepr.2026.101792_bib47","doi-asserted-by":"crossref","first-page":"995","DOI":"10.3390\/ijms25020995","article-title":"Anti-Obesity Effects of GABA in C57BL\/6J Mice with High-Fat Diet-Induced Obesity and 3T3-L1 Adipocytes","volume":"25","author":"Jin","year":"2024","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.jhepr.2026.101792_bib48","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.3390\/cells12172146","article-title":"GABA Prevents Age-Related Sarcopenic Obesity in Mice with High-Fat-Diet-Induced Obesity","volume":"12","author":"Jin","year":"2023","journal-title":"Cells"},{"key":"10.1016\/j.jhepr.2026.101792_bib49","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1002\/2211-5463.13817","article-title":"Structural investigations on the mitochondrial uncouplers niclosamide and FCCP","volume":"14","author":"Ng","year":"2024","journal-title":"FEBS Open Bio"}],"container-title":["JHEP Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589555926000637?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589555926000637?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T01:50:48Z","timestamp":1779414648000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589555926000637"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["S2589555926000637"],"URL":"https:\/\/doi.org\/10.1016\/j.jhepr.2026.101792","relation":{},"ISSN":["2589-5559"],"issn-type":[{"value":"2589-5559","type":"print"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A thioacrylamide-based compound directly counteracts hepatic fibrosis with profound anti-obesity action","name":"articletitle","label":"Article Title"},{"value":"JHEP Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jhepr.2026.101792","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).","name":"copyright","label":"Copyright"}],"article-number":"101792"}}