Glucocorticoids increase basal lipolysis, but not epinephrine stimulated lipolysis

Glucocorticoids (GCs) are associated with central obesity, yet have been classically defined as lipolytic. We have recently shown that exercise training decreases fat mass while increasing GC action in adipocytes, perhaps by increasing adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL). From this, we hypothesize that the lipolytic effects of GCs are mediated through changes in these adipose enzymes. To test this, we treated 3T3‐L1 adipocytes with GCs for 48 hours, and then allowed the cells to undergo basal or epinephrine stimulated lipolysis. 48 hours of GCs modestly increased lipolytic rates (1.6 fold vs con, p<0.05). However, the basal lipolysis following GC treatment was substantially increased (3.5 fold vs. con, p<0.01). The expression of ATGL was increased 3.5 fold over control (p<0.01), whereas HSL expression was increased only 1.5 fold (p<0.05). The phosphorylation of HSL at Ser563 and Ser660, sites that increase HSL activity, were also increased significantly (4.5‐and 2.2‐fold vs con, respectively; p<0.01). GC treatment only modestly increased epinephrine stimulated lipolysis (1.5 fold vs con, p<0.05). The phosphorylation of HSL at Ser563 and Ser565 by epinephrine was not affected by GC treatment. Thus, it appears GCs influence lipolysis mainly through alterations in basal lipolysis predominantly by altering ATGL expression and HSL activity. Supported by NSERC and CIHR.