Kashikawa_2026_Biochem.Biophys.Res.Commun_829_154175

Ambra1, a key regulator of protein homeostasis, controls both autophagy and ubiquitin-mediated proteasomal degradation. Although Ambra1 is implicated in metabolic regulation, its role in adipose tissue homeostasis remains unclear. In this study, Ambra1 conditional knockout mice exhibited impaired fasting-induced weight loss in white adipose tissue. Ambra1-deficient adipocytes exhibited defective lipolysis, accompanied by impaired translocation of adipose triglyceride lipase (ATGL), the rate-limiting lipolytic enzyme, to the surface of lipid droplets. However, ATGL translocation was restored by the inhibition of phosphodiesterase 3B, which antagonizes lipolysis by reducing protein kinase A activity. Collectively, these findings suggest that Ambra1 plays an important role in fasting-induced lipolysis via phosphodiesterase 3B-mediated ATGL control.