Regulation of HSL and ATGL activity

Basal conditions: The lipid droplet associated protein perilipin A functions as a barrier that protects TAG from hydrolysis and interacts with the protein CGI-58 at the lipid droplet surface

Activation: The main pathway for activation of lipolysis is via catecholamines. These lipolytic hormones interact with β-adrenergic receptors that promote 3’,5’-cyclic adenosine monophosphate (cAMP)-mediated activation of protein kinase (PK)A (not shown). PKA then phosphorylates HSL and perilipin A. Phosphorylation of perilipin A inhibits its interaction with the protein CGI-58 and CGI-58 dissociates to form a complex with ATGL. CGI-58 has been shown to be a co-factor for ATGL, but not HSL and is necessary for ATGL activity. Phosphorylation of HSL results in translocation from the cytosol to the lipid droplet surface, where it catalyses hydrolysis (10).

Inhibition: The main hormone involved in inhibition of lipolysis is insulin. Insulin signals through its receptor tyrosine kinase, which recruits and phosphorylates insulin receptor substrate (IRS)-1. IRS-1 then recruits downstream signalling molecules, including phosphoinositide 3-kinase (PI3K), which phosphorylates phosphatidylinositol at the 3 position of the inositol ring. PKB is recruited to the membrane through its plecstrin homology domain, which binds to phosphatydylinositol-3,4,5-triphosphate with high affinity. PKB is subsequently phosphorylated and activated by PDK1 and can thus phosphorylate two important targets for down-regulation of lipolysis: Phosphodiesterase 3B and protein phosphatase 2A, 2C and 1. Phosphodiesterase 3B hydrolyses cAMP to form 5’AMP and thus decreases PKA activation, whereas protein phosphatase 2A, 2C and 1 dephosphorylates HSL and perilipin (only the final effects are shown) (10).

Abbreviations: ATGL, adipose triacylglyceride lipase; DAG, diacylglycerol; FA, fatty acid; HSL, hormone sensitive lipase; per A, perilipin A; TAG, triacylglycerol

Hydrolyse af triacylglycerol

  • Videnskabelige figurer

Reguleringen af nedbrydningen af fedt.