Fat Mobilization in Adipose Tissue Is Promoted by Adipose Triglyceride Lipase

TLDR

Lipolysis of triglycerides in adipose tissue is essential for energy homeostasis, with hormone‑sensitive lipase previously considered the sole enzyme, but recent evidence shows that adipose triglyceride lipase also plays a key role. We demonstrate that adipose triglyceride lipase catalyzes the first step of triglyceride hydrolysis and that its inhibition markedly reduces total acyl‑hydrolase activity in adipose tissue.

Abstract

Mobilization of fatty acids from triglyceride stores in adipose tissue requires lipolytic enzymes. Dysfunctional lipolysis affects energy homeostasis and may contribute to the pathogenesis of obesity and insulin resistance. Until now, hormone-sensitive lipase (HSL) was the only enzyme known to hydrolyze triglycerides in mammalian adipose tissue. Here, we report that a second enzyme, adipose triglyceride lipase (ATGL), catalyzes the initial step in triglyceride hydrolysis. It is interesting that ATGL contains a "patatin domain" common to plant acyl-hydrolases. ATGL is highly expressed in adipose tissue of mice and humans. It exhibits high substrate specificity for triacylglycerol and is associated with lipid droplets. Inhibition of ATGL markedly decreases total adipose acyl-hydrolase activity. Thus, ATGL and HSL coordinately catabolize stored triglycerides in adipose tissue of mammals.