Genistein relieves liver damage and improves lipid dysregulation through endoplasmic reticulum suppression in nonalcoholic steatohepatitis rats

Abstract

In this study, we investigated the potential of genistein, the most abundant isoflavone in soybeans, to mitigate endoplasmic reticulum (ER) stress in high-fat high-sucrose induced nonalcoholic steatohepatitis (NASH) rats. Forty male SD rats are divided into four groups: the Control group, high-fat high-sucrose diet group (HFSD), HFSD + low-dose genistein group (LG), and HFSD + high-dose genistein group (HG). The Control group is fed with a D12450B diet, whereas the latter three groups are fed with a D12492 diet with 10% sucrose in drinking water. 12 weeks later, serum and liver lipid levels, serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, and protein expression of GRP78, PKR-like ER kinase (PERK), p-PERK, eukaryotic initiation factor (eIF2α), p-eIF2α and C/EBP homologous protein (CHOP) were characterized. Genistein significantly improved lipid profiles, alleviated AST and ALT levels, and reduced key typical NASH features, including macrovascular steatosis, lobular inflammation, and balloon degeneration of hepatocytes. Furthermore, our results demonstrated that genistein suppressed the activation of PERK-eIF2α-CHOP signal pathway induced by HFSD. Our present study indicates that genistein is capable of relieving liver damage, improving lipid dysregulation and modulating ER stress by suppressing the activation of the PERK-eIF2α-CHOP signal pathway in NASH rats.

Practical Applications: Genistein is capable to relieve liver damage and improve lipid dysregulation through the modulation of PERK–eIF2α–CHOP in NASH rats.