Endoplasmic reticulum (ER) stress could participate in high-fat diet (HFD)-induced hepatic steatosis. The current study aims to investigate the role of ER stress as well as inflammation as possible pathophysiologic mechanisms of HFD-induced hepatic steatosis at ultrastructure and molecular levels. Fifteen control rats on ordinary diet and 30 HFD-fed rats were enrolled in the study. Histological and EM examinations of rats' liver were carried out. Molecular study of TNF-α, CRP, and HNF4α by RT qPCR as well as biochemical investigation of liver function and lipids profile were done. Hepatic steatosis was induced with lipid droplets accumulation at histological level and mega-mitochondria with reduced ER-mitochondrial distance at EM level. Increased gene expression of TNF-α and CRP was significantly correlated with the reduced HNF4α expression and with other ER stress markers. In conclusion, endoplasmic reticulum stress, confirmed at ultrastructure level, plays an important role in pathogenesis of HFD-induced hepatic steatosis. HNF4α downregulation as well as increased expression of hs-CRP and TNF-α enforce the concept of interplay between ER stress, hepatic subclinical inflammation, and disturbed gene expression regulation in the pathogenesis of HFD-induced hepatic steatosis.

中文翻译：

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肝脂肪变性中内质网应激的分子和超微结构研究：肝细胞核因子4α和炎症介质的作用。

内质网应激可能参与高脂饮食诱导的肝脂肪变性。当前的研究旨在在超微结构和分子水平上研究内质网应激和炎症以及HFD诱导的肝脂肪变性的可能病理生理机制。该研究招募了15只普通饮食的对照大鼠和30只HFD喂养的大鼠。进行了大鼠肝脏的组织学和EM检查。通过RT qPCR对TNF-α，CRP和HNF4α进行了分子研究，并进行了肝功能和血脂谱的生化研究。肝脂肪变性的发生是由于组织学水平的脂滴积累和巨线粒体，而在EM水平的ER线粒体距离减小。TNF-α和CRP的基因表达增加与HNF4α的减少以及其他ER应激标志物显着相关。总之，在超微结构水平上证实的内质网应激在HFD诱发的肝脂肪变性的发病机理中起着重要作用。HNF4α的下调以及hs-CRP和TNF-α的表达增加，在HFD所致肝脂肪变性的发病机理中，强调了内质网应激，肝亚临床炎症和基因表达调控紊乱之间的相互作用。