Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome "Foro Italico,", Rome, Italy.
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
Hepatology. 2020 Aug;72(2):470-485. doi: 10.1002/hep.31056. Epub 2020 May 22.
Lipopolysaccharides (LPS) is increased in nonalcoholic fatty liver disease (NAFLD), but its relationship with liver inflammation is not defined.
We studied Escherichia coli LPS in patients with biopsy-proven NAFLD, 25 simple steatosis (nonalcoholic fatty liver) and 25 nonalcoholic steatohepatitis (NASH), and in mice with diet-induced NASH. NASH patients had higher serum LPS and hepatocytes LPS localization than controls, which was correlated with serum zonulin and phosphorylated nuclear factor-κB expression. Toll-like receptor 4 positive (TLR4 ) macrophages were higher in NASH than simple steatosis or controls and correlated with serum LPS. NASH biopsies showed a higher CD61 platelets, and most of them were TLR4 . TLR4 platelets correlated with serum LPS values. In mice with NASH, LPS serum levels and LPS hepatocyte localization were increased compared with control mice and associated with nuclear factor-κB activation. Mice on aspirin developed lower fibrosis and extent compared with untreated ones. Treatment with TLR4 inhibitor resulted in lower liver inflammation in mice with NASH.
In NAFLD, Escherichia coli LPS may increase liver damage by inducing macrophage and platelet activation through the TLR4 pathway.
非酒精性脂肪性肝病（NAFLD）患者的脂多糖（LPS）增加，但它与肝脏炎症的关系尚未明确。
我们研究了经活检证实的 NAFLD 患者、25 例单纯性脂肪性肝病（非酒精性脂肪肝）和 25 例非酒精性脂肪性肝炎（NASH）患者以及饮食诱导的 NASH 小鼠中的大肠杆菌 LPS。与对照组相比，NASH 患者的血清 LPS 和肝细胞 LPS 定位更高，与血清 zonulin 和磷酸化核因子-κB 表达相关。NASH 中 TLR4 阳性（TLR4 ）巨噬细胞高于单纯性脂肪性肝病或对照组，并与血清 LPS 相关。NASH 活检显示更高的 CD61 血小板，其中大多数为 TLR4 。TLR4 血小板与血清 LPS 值相关。与对照组相比，NASH 小鼠的血清 LPS 水平和 LPS 肝细胞定位增加，与核因子-κB 激活相关。与未治疗组相比，服用阿司匹林的小鼠的纤维化和程度降低。NASH 小鼠中 TLR4 抑制剂的治疗导致肝炎症降低。
在 NAFLD 中，大肠杆菌 LPS 可能通过 TLR4 途径诱导巨噬细胞和血小板激活，从而增加肝脏损伤。
