Alleviating effects of koji-fermented soybean extract on nonalcoholic steatohepatitis in mice through inactivation of acetyl-CoA carboxylase without inhibition of AMPK

Nonalcoholic steatohepatitis (NASH) is the most common cause of chronic liver disease. Here, we examined the effects of koji-fermented soy extract (KFS) on NASH model mice fed a methionine–choline-deficient (MCD) diet. The continuous administration of KFS significantly reduced the number of lipid droplets in the livers of MCD diet-fed mice and lowered the serum level of ALT. KFS also reduced the increased expression levels of the srebp and fasn genes, which are involved in fatty acid synthesis, in MCD-fed mice. The level of phosphorylated AMP-activated protein kinase α (p-AMPKα)was increased in the livers of MCD-fed mice and was attenuated by KFS administration. The level of phosphorylated acetyl-CoA carboxylase (p-ACC)was decreased in the livers of MCD-fed mice but was increased after KFS administration. These results suggest that KFS administration may promote the inactivation of ACC without inhibiting AMPK and treat NASH via the inhibition of fatty acid synthesis • Koji-fermented soybean extract (KFS) improved NASH pathogenesis in MCD-fed mice. • KFS reduced the lipid droplets and lowered the activity level of ALT in MCD-fed mice. • KFS suppressed upregulation of genes associated with fatty acid synthesis in MCD-fed mice. • KFS may promote inactivation of ACC, a fatty acid synthesis rate-limiting enzyme, in an AMPK-independent manner.