Invited Speaker ANZOS Annual Scientific Meeting 2021

Insulin Regulation of Lipolysis in Adipocytes (#59)

Jacqueline Stoeckli 1
  1. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia

Insulin suppresses adipose tissue lipolysis after a meal, playing a key role in metabolic homeostasis. This is mediated via the kinase Akt and its substrate phosphodiesterase 3B (PDE3B). Once phosphorylated and activated, PDE3B hydrolyses cAMP leading to the inactivation of cAMP-dependent protein kinase (PKA) and suppression of lipolysis. We recently identified a novel player in this process, the abhydrolase domain containing protein 15 (ABHD15) that interacts with PDE3B. We showed that in the absence of ABHD15, insulin is no longer able to suppress lipolysis, and ABHD15 knockout mice display unrestrained lipolysis, elevated plasma fatty acid levels and fatty liver in the presence of stress. ABHD15 deletion was associated with dysregulated PKA signalling on lipid droplets. We have new evidence that ABHD15 acts as a PDE3B repressor.  The regulated interaction between PDE3B and ABHD15 is mediated via Akt mediated phosphorylation and 14-3-3 binding and this plays a key role in regulating intracellular cAMP Levels setting the lipolytic tone of the fat cell.