Brown Adipose Tissue: Molecular Mechanisms of Regulation, Physiological Functions, and Therapeutic Targets

ABSTRACT Brown adipose tissue (BAT) biology has undergone a profound evolution over the past two decades, expanding from a narrow focus on thermogenic capacity in rodents to the establishment of its pleiotropic roles in human metabolic regulation. While this transition has enabled major progress in defining underlying molecular mechanisms and strengthened the clinical rationale for targeting BAT, it has also exposed unresolved challenges and knowledge gaps. In this review, we synthesize current evidence across the field, integrating findings from molecular, physiological, and translational studies to delineate the hierarchical regulatory networks that govern BAT development and function. We focus on three themes: first, the transcriptional, epigenetic, and posttranscriptional mechanisms that establish and maintain BAT identity; second, the expanding spectrum of BAT's physiological functions beyond thermogenesis, including its crosstalk with other metabolic organs and the immune system; and third, the emerging strategies and persistent obstacles in harnessing BAT's therapeutic potential for obesity, diabetes, and related metabolic disorders. By consolidating these perspectives, we propose an integrative framework for understanding BAT as a central hub in human metabolic regulation while identifying critical knowledge gaps that warrant further investigation.