Inzaugarat María Eugenia, De Matteo Elena, Baz Placida, Lucero Diego, García Cecilia Claudia, Gonzalez Ballerga Esteban, Daruich Jorge, Sorda Juan Antonio, Wald Miriam Ruth, Cherñavsky Alejandra Claudia
Instituto de Inmunología, Genética y Metabolismo-CONICET- Universidad de Buenos Aires, Buenos Aires, Argentina.
Hospital de Niños "Dr. R. Gutiérrez", Servicio de Patología, Buenos Aires, Argentina.
PLoS One. 2017 Mar 3;12(3):e0172900. doi: 10.1371/journal.pone.0172900. eCollection 2017.
The immune system acts on different metabolic tissues that are implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Leptin and linoleic acid have the ability to potentially affect immune cells, whereas curcumin is a known natural polyphenol with antioxidant and anti-inflammatory properties.
This study was designed to evaluate the pro-inflammatory and pro-oxidant effects of leptin and linoleic acid on immune cells from patients with NAFLD and to corroborate the modulatory effects of curcumin and its preventive properties against the progression of NAFLD using a high-fat diet (HFD)-induced NAFLD/nonalcoholic steatohepatitis mouse model.
The ex vivo experiments showed that linoleic acid increased the production of reactive oxygen species in monocytes and liver macrophages, whereas leptin enhanced tumor necrosis factor-α (TNF-α) production in monocytes and interferon-γ production in circulating CD4+ cells. Conversely, oral administration of curcumin prevented HFD-induced liver injury, metabolic alterations, intrahepatic CD4+ cell accumulation and the linoleic acid- and leptin- induced pro-inflammatory and pro-oxidant effects on mouse liver macrophages.
Our findings provide new evidence for the therapeutic potential of curcumin to treat human NAFLD. However, the development of a preventive treatment targeting human circulating monocytes and liver macrophages as well as peripheral and hepatic CD4+ cells requires additional research.
免疫系统作用于与非酒精性脂肪性肝病(NAFLD)发病机制相关的不同代谢组织。瘦素和亚油酸有潜在影响免疫细胞的能力,而姜黄素是一种已知的具有抗氧化和抗炎特性的天然多酚。
本研究旨在评估瘦素和亚油酸对NAFLD患者免疫细胞的促炎和促氧化作用,并使用高脂饮食(HFD)诱导的NAFLD/非酒精性脂肪性肝炎小鼠模型,证实姜黄素的调节作用及其对NAFLD进展的预防特性。
体外实验表明,亚油酸增加单核细胞和肝巨噬细胞中活性氧的产生,而瘦素增强单核细胞中肿瘤坏死因子-α(TNF-α)的产生以及循环CD4+细胞中干扰素-γ的产生。相反,口服姜黄素可预防HFD诱导的肝损伤、代谢改变、肝内CD4+细胞积聚以及亚油酸和瘦素对小鼠肝巨噬细胞的促炎和促氧化作用。
我们的研究结果为姜黄素治疗人类NAFLD的治疗潜力提供了新证据。然而,开发针对人类循环单核细胞和肝巨噬细胞以及外周和肝内CD4+细胞的预防性治疗方法还需要进一步研究。