Decoding Adipose Tissue Phenotypic Switching: From Mechanisms to Computational Drug Discovery

This review aims to explore the therapeutic potential of brown adipose tissue (BAT) to combat obesity and associated metabolic disorders by synthesizing the multifactorial influences and underlying mechanisms of BAT whitening and employing computational screening to identify promising candidate molecules for further investigation. BAT whitening is characterized by the loss of thermogenic capacity, representing a critical aspect of adipose plasticity. Although diverse physiological and environmental triggers have been identified, the mechanistic interconnections underlying this process remain poorly understood. Emerging evidence supports an integrated view of these factors, and bioinformatic approaches now provide a valuable tool for the preliminary screening of potential intervention candidates. This review synthesizes current understanding on BAT whitening, from influencing factors to mechanistic pathways. Mitochondrial dysfunction appears to be a critical hub that could link diverse triggers to downstream metabolic and functional decline. Through bioinformatic screening, 4-hydroxybenzoic acid (4-HBA) is proposed as a candidate worthy of further study. Future work should prioritize experimental validation to clarify its mechanism and assess its translational potential.