Porcine liver peptide ameliorates ethanol-induced liver injury via the NQO1 and ACAA1 signaling pathway through regulating oxidative stress and lipid metabolism

Alcoholic fatty liver disease (AFLD) is considered as an initial stage in the development of alcoholic liver disease. The benefit of porcine liver hydrolysates (PLH) and porcine liver peptide (NTLPHPTAP) on AFLD was demonstrated in vitro HepG-2 cell model as well as in vivo C57BL/6J mice model. After PLH and NTLPHPTAP treatment, the reactive oxygen species (ROS) level, triglyceride (TG), and liver injury markers, including aspartate transaminase (AST) and alanine transaminase (ALT) were ameliorated. The result of transcriptomics reminded that the main functional pathways of PLH and NTLPHPTAP were enriched in oxidative phosphorylation and fatty acid metabolism. Further validation of pathway proteins found that NTLPHPTAP regulated oxidative stress levels and mitochondrial function by increasing NQO1 expression. Metabolism of fatty acid β-oxidation in mitochondria was increased via PLH and NTLPHPTAP treatment by ACAA1 regulation, which attenuated intracellular lipid deposition. In conclusion, PLH and NTLPHPTAP may be bioactive compounds for the application of AFLD treatment or alleviation.