Ferulic Acid Mediates Metabolic Syndrome via the Regulation of Hepatic Glucose and Lipid Metabolisms and the Insulin/IGF-1 Receptor/PI3K/AKT Pathway in Palmitate-Treated HepG2 Cells.

Ferulic acid (FA) is one of the most abundant bound phenolics in whole grains, partly contributing to its preventive effects on metabolic syndrome (MetS). The study aims to investigate if FA mediates MetS through the regulation of hepatic metabolisms and the insulin receptor related pathways in the palmitate-treated HepG2 cells (MetS model). We found that FA (50, 100, and 200 µM) dramatically ameliorated the lipid accumulation in the MetS model. FA significantly decreased the activities of the gluconeogenic enzymes, G6Pase and PEPCK, downregulated the lipogenic enzyme FAS-1, and upregulated the lipolytic enzyme CPT-1 by regulating a series of transcriptional factors including HNF4α, FOXO-1, SREBP-1c, and PPAR-γ. Notably, we found that FA's ability to alleviate MetS is achieved by activating the insulin receptor/PI3K/AKT pathway. Our results validated the effects of FA on mediating the metabolic disorders of lipid and glucose pathways and unveiled its potential intracellular mechanisms for the prevention of MetS.