biostudies-literaturePadilla JNational Institute of Environmental Health SciencesDuke Cancer InstituteNational Institute of Diabetes and Digestive and Kidney DiseasesNIDDK NIH HHSNIEHS NIH HHSNIMHD NIH HHSNational Cancer InstituteU.S. Public Health ServiceNCI NIH HHSNational Institutes of HealthNational Institute on Minority Health and Health DisparitiesCancer Prevention and Research Institute of Texas282-292https://www.ebi.ac.uk/biostudies/studies/S-EPMC10929560biostudies-literatureUnknown80(2)<h4>Background & aims</h4>Chronic circadian dysfunction increases the risk of non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC), but the underlying mechanisms and direct relevance to human HCC have not been established. In this study, we aimed to determine whether chronic circadian dysregulation can drive NAFLD-related carcinogenesis from human hepatocytes and human HCC progression.<h4>Methods</h4>Chronic jet lag of mice with humanized livers induces spontaneous NAFLD-related HCCs from human hepatocytes. The clinical relevance of this model was analysed by biomarker, pathological/histological, genetic, RNA sequencing, metabolomic, and integrated bioinformatic analyses.<h4>Results</h4>Circadian dysfunction induces glucose intolerance, NAFLD-associated human HCJournal of hepatologyCircadian dysfunction induces NAFLD-related human liver cancer in a mouse model.PMC10929560RP200504CA125123P50MD015496R01 CA238988P30 ES030285RP210227R01 DK121970MIRA RP150587P30 CA125123P30 CA014236P50 MD015496506 DK563381P42 ES0327725P30 DK056338R01 CA230848R01 DK115461Padilla JGrimm SLYang LCoarfa CBissig-Choisat BLi FQin XMoore DDBissig KDOsman NMMajor AMLopez-Terrada DFu LfalseCircadian dysfunction induces NAFLD-related human liver cancer in a mouse model.<h4>Background & aims</h4>Chronic circadian dysfunction increases the risk of non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC), but the underlying mechanisms and direct relevance to human HCC have not been established. In this study, we aimed to determine whether chronic circadian dysregulation can drive NAFLD-related carcinogenesis from human hepatocytes and human HCC progression.<h4>Methods</h4>Chronic jet lag of mice with humanized livers induces spontaneous NAFLD-related HCCs from human hepatocytes. The clinical relevance of this model was analysed by biomarker, pathological/histological, genetic, RNA sequencing, metabolomic, and integrated bioinformatic analyses.<h4>Results</h4>Circadian dysfunction induces glucose intolerance, NAFLD-associated human HC2024-01-01T00:00:00Z2024 Feb2025-04-21T23:54:28.079Z2025-04-05T19:20:14.765ZS-EPMC109295603789072010.1016/j.jhep.2023.10.018