Talamantes Stephanie, Lisjak Michela, Gilglioni Eduardo H, Llamoza-Torres Camilo J, Ramos-Molina Bruno, Gurzov Esteban N
Signal Transduction and Metabolism Laboratory, Laboratoire de Gastroentérologie Expérimental et Endotools, Université Libre de Bruxelles, Route de Lennik 808, Brussels, 1070, Belgium.
Department of Hepatology, Virgen de la Arrixaca University Hospital, Murcia, 30120, Spain.
JHEP Rep. 2023 Jun 9;5(9):100811. doi: 10.1016/j.jhepr.2023.100811. eCollection 2023 Sep.
Obesity-related complications such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) are well-established risk factors for the development of hepatocellular carcinoma (HCC). This review provides insights into the molecular mechanisms that underlie the role of steatosis, hyperinsulinemia and hepatic inflammation in HCC development and progression. We focus on recent findings linking intracellular pathways and transcription factors that can trigger the reprogramming of hepatic cells. In addition, we highlight the role of enzymes in dysregulated metabolic activity and consequent dysfunctional signalling. Finally, we discuss the potential uses and challenges of novel therapeutic strategies to prevent and treat NAFLD/T2D-associated HCC.
肥胖相关并发症,如非酒精性脂肪性肝病(NAFLD)和2型糖尿病(T2D),是肝细胞癌(HCC)发生的公认危险因素。本综述深入探讨了脂肪变性、高胰岛素血症和肝脏炎症在HCC发生发展中作用的分子机制。我们重点关注了将细胞内信号通路和转录因子与肝细胞重编程联系起来的最新研究结果。此外,我们强调了酶在代谢活性失调及随之而来的信号功能障碍中的作用。最后,我们讨论了预防和治疗NAFLD/T2D相关HCC的新型治疗策略的潜在用途和挑战。