Peptides Obtained by Enzymatic Decomposition of Mackerel Prevent Nonalcoholic Steatohepatitis in Sprague-Dawley Rats fed a High-fat and High-cholesterol Diet

Abstract

Background: The pathogenesis of nonalcoholic steatohepatitis (NASH) is thought to be multifactorial, and oxidative stress may play an important role in the development of NASH. Peptides obtained by enzymatic decomposition of mackerel (EMP) including selenoneine were recently reported to possess antioxidative activity. Thus, EMP can be a candidate dietary strategy for the prevention of NASH. Methods: Nine-week-old male Sprague-Dawley rats were fed a high-fat and high-cholesterol (HFC) diet with or without EMP (10, 25, 50g/kg diet, or control) for 9 weeks (n=6-7/group). Histopathology, serology and expressions of fibrogenetic, proinflammatory, oxidative stress and lipid metabolism-related genes in the liver were evaluated. Results: Histologically, the HFC diet with EMP tended to reduce definite NASH progression compared to the HFC diet without EMP (NASH diagnostic rate: 80% vs 100%). Serum leptins in rats fed the HFC diet with EMP tended to be lower than those in rats fed an HFC diet without EMP. Immunohistochemically, the expression of 4-hydroxynonenal as a marker of oxidative stress in the liver tended to be less evident in rats fed the HFC diet with EMP than without EMP. mRNA levels of NF-κB tended to be lower in rats fed the HFC diet with EMP than without EMP, whereas mRNA levels of GPX-1 tended to be higher in rats fed the HFC diet with EMP than without EMP in an EMP-dose dependent manner. Histological findings and hepatic mRNA expressions indicate that the HFC diet containing 1% or 2.5% (w/w) EMP was more likely to reveal a preventive effect against NASH progression than the HFC diet with 5% (w/w) EMP. Conclusions: Our data suggest that EMP including selenoneine may prevent NASH progression, presumably through its antioxidative activity. The optimal dose of EMP requires further study.