The impact of cortisol in steatotic and non-steatotic liver surgery Cornide Petronio, María Eugenia Bujaldon, Esther Mendes-Braz, Mariana Avalos de León, Cindy G Jiménez Castro, Mónica B. Álvarez Mercado, Ana Isabel Gracia-Sancho, Jordi Rodés, Juan Peralta, Carmen Partial hepatectomy Acetylcholine Cortisol This research was supported by the Ministerio de Economía y Competitividad (MINECO) (SAF-2015-64857-R) Madrid, Spain, by the European Union (Fondos Feder, ‘una manera de hacer Europa’), by CERCA Program/Generalitat de Catalunya, and by the Secretaria d'Universitats i Recerca (SGR2014-144) Barcelona, Spain. MECP has received a Sara Borrell postdoctoral contract from ISCIII, Madrid, Spain, and CGAL is the recipient of a fellowship from CONACYT, México. MBJC also has a contract from EMPLEA Program-MINECO, Madrid, Spain, and JGS has a contract from the Programa Ramón y Cajal-MINECO, Madrid, Spain. We thank Michael Maudsley of the Language Advisory Service at the University of Barcelona and our copy editor at Bioscience Writers for English text revisions. We are indebted to the Bioinformatics core facility of the IDIBAPS for the technical help. The intent of this study was to examine the effects of regulating cortisol levels on damage and regeneration in livers with and without steatosis subjected to partial hepatectomy under ischaemia-reperfusion. Ultimately, we found that lean animals undergoing liver resection displayed no changes in cortisol, whereas cortisol levels in plasma, liver and adipose tissue were elevated in obese animals undergoing such surgery. Such elevations were attributed to enzymatic upregulation, ensuring cortisol production, and downregulation of enzymes controlling cortisol clearance. In the absence of steatosis, exogenous cortisol administration boosted circulating cortisol, while inducing clearance of hepatic cortisol, thus maintaining low cortisol levels and preventing related hepatocellular harm. In the presence of steatosis, cortisol administration was marked by a substantial rise in intrahepatic availability, thereby exacerbating tissue damage and regenerative failure. The injurious effects of cortisol were linked to high hepatic acethylcholine levels. Upon administering an α7 nicotinic acethylcholine receptor antagonist, no changes in terms of tissue damage or regenerative lapse were apparent in steatotic livers. However, exposure to an M3 muscarinic acetylcholine receptor antagonist protected livers against damage, enhancing parenchymal regeneration and survival rate. These outcomes for the first time provide new mechanistic insight into surgically altered steatotic livers, underscoring the compelling therapeutic potential of cortisol-acetylcholine-M3 muscarinic receptors. 2026-01-13T09:06:19Z 2026-01-13T09:06:19Z 2017-10-21 journal article Cornide-Petronio ME, Bujaldon E, Mendes-Braz M, Avalos de León CG, Jiménez-Castro MB, Álvarez-Mercado AI, Gracia-Sancho J, Rodés J, Peralta C. The impact of cortisol in steatotic and non-steatotic liver surgery. J Cell Mol Med. 2017 Oct;21(10):2344-2358. doi: 10.1111/jcmm.13156 1582-4934 1582-1838 https://hdl.handle.net/10481/109595 10.1111/jcmm.13156 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Wiley