Department of Hepatobiliary Surgery, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, China.
Department of Hepatobiliary Surgery, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, China.
Biochem Biophys Res Commun. 2019 Aug 20;516(2):584-590. doi: 10.1016/j.bbrc.2019.06.104. Epub 2019 Jun 22.
Nonalcoholic fatty liver disease (NAFLD) is a severe liver disease, which influences the health of people worldwide. However, the mechanism modulating the pathogenesis of NAFLD remains elusive. It was reported that nuclear enriched abundant transcript 1 (NEAT1) and microRNA-140 (miR-140) could regulate lipogenesis, but whether they could influence NAFLD are still unknown.
HepG2 cells were treated by free fatty acids (FFA) to establish the model of NAFLD in vitro, and C57 mice were treated by high-fat diet to establish the model of NAFLD in vivo. Cell transfection was applied to regulate the expression of NEAT1 and miR-140. Western blotting and qRT-PCR were applied for measuring expression of protein and mRNA, respectively. HE staining and Oil Red O staining were used for observing liver tissues.
NEAT1 and miR-140 are upregulated in hepacytes under the NAFLD conditions. NEAT1 directly binds to miR-140 and acts synergistically with miR-140 to exacerbate the progression of NAFLD. Reciprocally, silence of miR-140 or NEAT1 alleviates the severity of NAFLD. The mechanistical study shows that the axis of NEAT1-miR-140 inactivates AMPK/SREBP-1 signaling during the NAFLD. .
The NEAT1-miR-140 axis play a crucial role in modulation of NAFLD via inactivation of AMPK/SREBP1 signaling. This study may provide a novel insight for the treatment of NAFLD.
非酒精性脂肪性肝病（NAFLD）是一种严重的肝脏疾病，影响着全球人类的健康。然而，调节 NAFLD 发病机制的机制仍不清楚。有报道称核富集丰富转录本 1（NEAT1）和 microRNA-140（miR-140）可以调节脂肪生成，但它们是否会影响 NAFLD 尚不清楚。
用游离脂肪酸（FFA）处理 HepG2 细胞，在体外建立 NAFLD 模型，用高脂饮食处理 C57 小鼠，在体内建立 NAFLD 模型。采用细胞转染调节 NEAT1 和 miR-140 的表达。采用 Western blot 和 qRT-PCR 分别检测蛋白和 mRNA 的表达。采用 HE 染色和油红 O 染色观察肝组织。
在 NAFLD 条件下，肝细胞中 NEAT1 和 miR-140 表达上调。NEAT1 可直接与 miR-140 结合，并与 miR-140 协同作用，加重 NAFLD 的进展。相反，沉默 miR-140 或 NEAT1 可减轻 NAFLD 的严重程度。机制研究表明，NEAT1-miR-140 轴在 NAFLD 过程中通过抑制 AMPK/SREBP-1 信号通路起作用。
NEAT1-miR-140 轴通过抑制 AMPK/SREBP1 信号通路在调节 NAFLD 中起关键作用。本研究可能为 NAFLD 的治疗提供新的思路。
