Targeting Nuclear Import of Thyroid Hormone Receptor Alpha with Natural Polyphenols: Potential Mechanism for Lipolysis in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by excessive liver lipids and metabolic imbalance. Thyroid hormone receptor alpha (THRA) is essential for liver lipolysis; however, its transcription function is dependent on successful nuclear localization. Since natural polyphenols are known to modulate THRA activity, making them potential candidates for MASLD management, their roles in THRA nuclear trafficking have not been elucidated. In this study, an integrative computational method was utilized to investigate the impact of polyphenol binding on THRA nuclear import. Protein-protein docking simulations suggested that polyphenol binding may augment the interaction of THRA and importin-α, while importin-7 was predicted to be essential for basal transport. In conclusion, our findings showed that polyphenol binding could potentially support THRA nuclear import, thus potentially implicating a new process in MASLD.