Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Facultad de Medicina Pontificia Universidad Católica de Chile, Santiago, Chile; Escuela de Nutrición y Dietética, Facultad de Farmacia, Universidad de Valparaíso, Valparaíso, Chile.
Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
Nutr Res. 2022 Aug;104:71-81. doi: 10.1016/j.nutres.2022.04.005. Epub 2022 Apr 29.
Advanced glycation end products (AGEs) may be associated with nonalcoholic fatty liver disease (NAFLD) from stimulation of oxidative stress, inflammation, and fibrosis. We hypothesized that patients with NAFLD would have a lower concentration of soluble AGEs receptor and higher quantity of serum and liver AGEs and an increase in hepatic smooth muscle actin alpha (α-SMA) and transforming growth factor beta 1 (TGF-β1) compared with a control group. We compared the presence of hepatic and serum AGEs, AGE soluble receptor (sRAGE), and markers associated with hepatic damage between NAFLD patients and controls without disease. Histological characteristics, plasma biochemical parameters, serum AGEs, serum receptor sRAGE, and liver proteins (α-SMA, TGF-β1, AGEs, immunohistochemistry) were assessed in participants aged 18 to 65 years, with NAFLD (simple steatosis [SS]: n = 7; steatohepatitis [NASH]: n = 15) and controls (n = 11). NASH patients presented higher glycated hemoglobin levels (%) (5.7; 5.4-6.3) compared with SS (5.4; 5.2-5.7) and controls (5.4; 5.3-5.5). The NAFLD activity score (NAS) for NASH patients was 4.9 ± 1.3; for SS patients, 2.0 ± 1.0. NASH patients showed higher hepatic AGEs, TGF-β1, and α-SMA compared with SS and control groups. The NAS score indicates that patients with 5 to 8 had higher hepatic AGEs, TGF-β1, and α-SMA compared with a NAS of 1 to 4 and 0. For α-SMA, a NAS of 1 to 4 was higher than NAS 0. No difference was found in serum AGEs and sRAGE between groups. Higher hepatic AGEs, TGF-β1, and α-SMA were observed with increasing disease severity (according to NAS); therefore, endogenous liver AGEs may participate in hepatic damage progression.
晚期糖基化终产物 (AGEs) 可能通过刺激氧化应激、炎症和纤维化与非酒精性脂肪性肝病 (NAFLD) 有关。我们假设，与对照组相比，NAFLD 患者可溶性 AGE 受体浓度较低，血清和肝脏 AGEs 含量较高，肝平滑肌肌动蛋白α (α-SMA) 和转化生长因子β 1 (TGF-β1) 增加。我们比较了 NAFLD 患者和无疾病对照组之间肝组织和血清 AGEs、AGE 可溶性受体 (sRAGE) 以及与肝损伤相关的标志物的存在情况。评估了年龄在 18 至 65 岁之间的参与者的组织学特征、血浆生化参数、血清 AGEs、血清受体 sRAGE 和肝蛋白 (α-SMA、TGF-β1、AGEs、免疫组织化学)，包括单纯性脂肪变性 [SS] (n=7) 和非酒精性脂肪性肝炎 [NASH] (n=15) 的 NAFLD 患者和对照组 (n=11)。与 SS (5.4；5.2-5.7) 和对照组 (5.4；5.3-5.5) 相比，NASH 患者的糖化血红蛋白水平 (%) 较高 (5.7；5.4-6.3)。NASH 患者的 NAFLD 活动评分 (NAS) 为 4.9 ± 1.3；SS 患者为 2.0 ± 1.0。与 SS 和对照组相比，NASH 患者的肝 AGEs、TGF-β1 和 α-SMA 更高。NAS 评分表明，5 至 8 分的患者肝 AGEs、TGF-β1 和 α-SMA 高于 1 至 4 分和 0 分。对于 α-SMA，1 至 4 分的 NAS 高于 0 分。各组间血清 AGEs 和 sRAGE 无差异。随着疾病严重程度的增加 (根据 NAS)，观察到更高的肝 AGEs、TGF-β1 和 α-SMA；因此，内源性肝 AGEs 可能参与肝损伤的进展。
