Molecular and ultrastructure study of endoplasmic reticulum stress in hepatic steatosis: role of hepatocyte nuclear factor 4α and inflammatory mediators

• Published in: Histochemistry and cell biology Vol. 153; no. 1; pp. 49 - 62
• Main Authors: Abo El-khair, Salwa M., Ghoneim, Fatma M., Shabaan, Dalia A., Elsamanoudy, Ayman Z.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 2020; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Developmental Biology; Diet, High-Fat - adverse effects; Disease Models, Animal; Endoplasmic reticulum; Endoplasmic Reticulum Stress; Fatty liver; Fatty Liver - metabolism; Gene expression; Gene regulation; Hepatocyte Nuclear Factor 4 - metabolism; High fat diet; Inflammation; Inflammation - metabolism; Inflammation - physiopathology; Inflammation Mediators - metabolism; Lipids; Male; Mitochondria; Original Paper; Pathogenesis; Rats; Rats, Sprague-Dawley; Steatosis; Tumor necrosis factor-α; Ultrastructure; CRP; Hepatic steatosis; TNF-α; HNF4α; High fat diet; Endoplasmic reticulum stress
• ISSN: 0948-6143; 1432-119X
• DOI: 10.1007/s00418-019-01823-2

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.