Faculty of Medicine, National Autonomous University of Mexico, Tlalpan, Mexico City 04510, Mexico.
Medical, Dental and Health Sciences Master and Doctorate Program, National Autonomous University of Mexico, Tlalpan, Mexico City 04510, Mexico.
Genes (Basel). 2023 Oct 13;14(10):1935. doi: 10.3390/genes14101935.
Gallstone disease and metabolic dysfunction-associated fatty liver disease (MAFLD) share numerous common risk factors and progression determinants in that they both manifest as organ-specific consequences of metabolic dysfunction. Nevertheless, the precise molecular mechanisms underlying fibrosis development in cholecystectomized MAFLD patients remain inadequately defined. This study aimed to investigate the involvement of farnesoid X receptor 1 (FXR1) and fibroblast growth factor receptor 4 (FGFR4) in the progression of fibrosis in cholecystectomized MAFLD patients. A meticulously characterized cohort of 12 patients diagnosed with MAFLD, who had undergone liver biopsies during programmed cholecystectomies, participated in this study. All enrolled patients underwent a follow-up regimen at 1, 3, and 6 months post-cholecystectomy, during which metabolic biochemical markers were assessed, along with elastography, which served as indirect indicators of fibrosis. Additionally, the hepatic expression levels of FGFR4 and FXR1 were quantified using quantitative polymerase chain reaction (qPCR). Our findings revealed a robust correlation between hepatic FGFR4 expression and various histological features, including the steatosis degree (r = 0.779, = 0.023), ballooning degeneration (r = 0.764, = 0.027), interphase inflammation (r = 0.756, = 0.030), and steatosis activity score (SAS) (r = 0.779, = 0.023). Conversely, hepatic FXR1 expression did not exhibit any significant correlations with these histological features. In conclusion, our study highlights a substantial correlation between FGFR4 expression and histological liver damage, emphasizing its potential role in lipid and glucose metabolism. These findings suggest that FGFR4 may play a crucial role in the progression of fibrosis in cholecystectomized MAFLD patients. Further research is warranted to elucidate the exact mechanisms through which FGFR4 influences metabolic dysfunction and fibrosis in this patient population.
胆石病和代谢相关脂肪性肝病（MAFLD）有许多共同的危险因素和进展决定因素，因为它们都表现为代谢功能障碍的器官特异性后果。然而，胆石切除的 MAFLD 患者纤维化发展的确切分子机制仍未得到充分定义。本研究旨在探讨法尼醇 X 受体 1（FXR1）和成纤维细胞生长因子受体 4（FGFR4）在胆石切除的 MAFLD 患者纤维化进展中的作用。本研究纳入了 12 例经程序胆囊切除术确诊为 MAFLD 并接受肝活检的患者。所有入组患者在胆囊切除术后 1、3 和 6 个月进行随访，评估代谢生化标志物和弹性成像，作为纤维化的间接指标。此外，还使用定量聚合酶链反应（qPCR）定量检测 FGFR4 和 FXR1 的肝表达水平。我们的研究结果显示，肝 FGFR4 表达与各种组织学特征之间存在显著相关性，包括脂肪变性程度（r = 0.779， = 0.023）、气球样变性（r = 0.764， = 0.027）、界面炎症（r = 0.756， = 0.030）和脂肪变性活动评分（SAS）（r = 0.779， = 0.023）。相反，肝 FXR1 表达与这些组织学特征之间没有显著相关性。总之，我们的研究强调了 FGFR4 表达与肝组织损伤之间存在显著相关性，表明其在脂质和糖代谢中的潜在作用。这些发现表明 FGFR4 可能在胆石切除的 MAFLD 患者纤维化进展中起关键作用。需要进一步研究以阐明 FGFR4 如何影响该患者人群的代谢功能障碍和纤维化的确切机制。
