<em>In Silico</em> Study of Natural Polyphenols as Potential Metabolic Modulators in Mitigating Lipotoxicity in Non-Alcoholic Fatty Liver Disease via Thyroid Hormone Receptor Alpha Activation

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder described by the deposition of triglycerides in the liver, which primarily occurs due to insulin resistance and obesity. Thyroid hormone receptor alpha (THRA) is involved in metabolic pathways that promote lipolysis, which can prevent the accumulation of liver fat. As a possible treatment for NAFLD, this in silico study examines the binding interactions between THRA and polyphenols and flavonoids present in fruits and vegetables. Including caffeic acid, curcumin, and chlorogenic acid, the binding affinities of the natural substances to THRA were found comparable to the hormone T3, boosting the THRA-TRAP220 complex, promoting fatty acid oxidation, while decreasing lipid accumulation in the liver.