Metformin counters both lipolytic/inflammatory agents-decreased hormone sensitive lipase phosphorylation at Ser-554 and -induced lipolysis in human adipocytes.

OBJECTIVE

To study the effects of metformin on lipolysis and hormone sensitive lipase (HSL) phosphorylation in human adipocytes treated with lipolytic and inflammatory agents.

METHODS

Lipolysis and phosphorylation status of HSL were assessed in subcutaneous pre-adipocytes surgically isolated from patients and differentiated into mature adipocytes in vitro.

RESULTS

Stimulation for 1 h with forskolin, isoproterenol and IBMX or stimulation for 24 h with LPS, IL-1β and TNF-α increased lipolysis (p < 0.05 vs. basal). The phosphorylation of HSL at Ser-554 was decreased while the Ser-552 phosphorylation was increased. Pre-incubation with metformin (24 h, 1 mM) inhibited forskolin-, isoproterenol-, IBMX-, LPS-, IL-1β- and TNF-α-induced glycerol release and prevented p(Ser554)HSL decrease and p(Ser-552)HSL increase due to lipolytic and inflammatory agents. AMPKα1 is involved in metformin-induced HSL phosphorylation at Ser-552.

CONCLUSIONS

Phosphorylation of HSL at Ser-554 inversely correlates with lipolysis and HSL phosphorylation at Ser552 in human adipocytes.