Myristoylated Eepd1 Enhances Lipolysis and Thermogenesis through PKA Activation to Combat Obesity

Middle-aged obesity, characterized by excessive fat accumulation and systemic energy imbalance, often precedes various health complications. Recent research has unveiled a surprising link between DNA damage response and energy metabolism. Here, we explore the role of Eepd1, a DNA repair enzyme, in regulating adipose tissue function and obesity onset. Eepd1 is primarily expressed in adipose tissue, where its downregulation or deletion accelerates obesity development. We show that Eepd1 ablation in vivo hinders PKA activation, thereby inhibiting lipolysis and thermogenesis in adipose tissue. leading to obesity progression and dysregulation of glucose metabolism. This study reveals Eepd1's unexpected role in promoting adipose lipolysis and thermogenesis, underscoring its potential as a promising therapeutic target to combat obesity. Overall design: RNA-seq profiling of white adipose tissue from WT and EKO mice after high-fat diet for 3 months.