Corn Oligopeptide Alleviates Nonalcoholic Fatty Liver Disease by Regulating the Sirtuin Signaling Pathway

Nonalcoholic fatty liver disease (NAFLD) represents the
most prevalent type of chronic liver disease, spanning from simple
steatosis to nonalcoholic steatohepatitis (NASH). Corn oligopeptide
(CP) is a functional peptide known for its diverse pharmacological
effects on metabolism. In this study, we evaluated the protective
activity of CP against fatty liver disease. Oral administration of
CP significantly reduced body weight gain by 2.95%, serum cholesterol
by 22.54%, and liver injury, as evidenced by a reduction of 32.19%
in serum aspartate aminotransferase (AST) and 49.10% in alanine aminotransferase
(ALT) levels in mice subjected to a high-fat diet (HFD). In a streptozotocin/HFD-induced
NASH mouse model, CP attenuated body weight gain by 5.11%, liver injury
(with a 34.15% decrease in AST and 11.43% decrease in ALT), and, to
some extent, liver inflammation and fibrosis. Proteomic analysis revealed
the modulation of oxidative phosphorylation and sirtuin (SIRT) signaling
pathways by CP. Remarkably, CP selectively inhibited the hepatic expression
of mitochondrial SIRT3 and SIRT5 in both HFD and NASH models. In summary,
CP demonstrates a preventive effect against metabolic-stress-induced
NAFLD progression by modulating oxidative stress and the SIRT signaling
pathway, suggesting the potential of CP as a therapeutic agent for
the treatment of NAFLD and advanced-stage NASH.