Adss1–HDAC3 Interaction: A Novel Mechanism for Epigenetic Regulation of Metabolism in Adipose Tissue

ABSTRACT Obesity and its related metabolic disorders have emerged as global public health challenges with underlying mechanisms involving an imbalance between energy storage and expenditure in the adipose tissue. In recent years, with the deepening research on adipose tissue metabolism, the cross talk between metabolic enzymes and epigenetic regulation has gradually attracted attention. Adenylate succinate synthase 1 (Adss1) has traditionally been regarded as a metabolic enzyme involved in de novo purine synthesis; however, recent studies have revealed its critical noncanonical function in adipose tissue energy metabolism. Adss1 can lower HDAC3 activity by interacting with histone deacetylase 3 (HDAC3) and influencing its nucleo‐cytoplasmic distribution, thereby affecting the epigenetic state of adipocytes. This discovery breaks the traditional perception that limits Adss1 to metabolic reactions. This article will focus on discussing the molecular mechanism of Adss1–HDAC3 interaction and briefly outline the potential role of HDAC3 nucleo‐cytoplasmic dynamic localization in adipose metabolism, providing a new conceptual framework for understanding the coupling between metabolic signaling and epigenetic regulation.