FERULIC ACID AS A POTENTIAL THERAPEUTICAL AGENT IN METABOLIC SYNDROME PREVENTION-MOLECULAR MECHANISM OF ACTION
Access to this document is restricted. Some items have been embargoed at the request of the author, but will be made publicly available after the "No Access Until" date.
During the embargo period, you may request access to the item by clicking the link to the restricted file(s) and completing the request form. If we have contact information for a Cornell author, we will contact the author and request permission to provide access. If we do not have contact information for a Cornell author, or the author denies or does not respond to our inquiry, we will not be able to provide access. For more information, review our policies for restricted content.
Metabolic syndrome (MetS) is a prevalent and multifaceted disorder characterized by the clustering of metabolic abnormalities, including insulin resistance, dyslipidemia, obesity, and chronic inflammation. These interconnected pathologies significantly increase the risk of developing life-threatening conditions like cardiovascular disease, type 2 diabetes, and metabolic dysfunction-associated fatty liver disease (MAFLD). The high prevalence of MetS is largely attributable to the overconsumption of nutrients associated with urban lifestyles. Consequently, there is an urgent need to explore therapeutic strategies addressing dietary interventions that can simultaneously target multiple aspects of MetS. Phenolic compounds, abundant in whole grains and medicinal plants, have garnered significant attention for their potential to combat metabolic diseases due to their antioxidant, anti-inflammatory, and metabolic regulatory properties. Our research aimed to elucidate the therapeutic effects of ferulic acid (FA), a prominent phenolic compound, on various pathological features of MetS using the palmitate-treated HepG2 hepatic cell line as an in vitro model. Our findings demonstrate that FA ameliorates insulin resistance, dyslipidemia, and gluconeogenesis by modulating the insulin/IGF-1 receptor/PI3K/AKT signaling pathway, thereby improving glucose and lipid metabolism. Additionally, FA counteracts mitochondrial dysfunction and impaired autophagy by restoring mitochondrial dynamics and promoting autophagic flux through the AMPK signaling pathway, ensuring cellular homeostasis. Notably, FA also regulates cell cycle progression and inflammation by inhibiting NF-κB signaling, reducing pro-inflammatory cytokine production, and regulating cell cycle-related proteins, thus mitigating palmitate-induced G1 cell cycle arrest and chronic inflammation. These multifaceted effects underscore FA's therapeutic potential in preventing and combating MetS.