A Peptide Derived from G0/G1 Switch Gene 2 Acts as Non-competitive Inhibitor of Adipose Triglyceride Lipase [Metabolism]

September 25th, 2014 by Cerk, I. K., Salzburger, B., Boeszoermenyi, A., Heier, C., Pillip, C., Romauch, M., Schweiger, M., Cornaciu, I., Lass, A., Zimmermann, R., Zechner, R., Oberer, M.

G0/G1 switch gene 2 (G0S2) is a small basic protein that functions as endogenous inhibitor of adipose triglyceride lipase (ATGL), a key enzyme in intracellular lipolysis. In this study, we identified a short sequence covering residues Lys20 to Ala52 in G0S2 that is still fully capable of inhibiting mouse and human ATGL. We found that a synthetic peptide corresponding to this region inhibits ATGL in a non-competitive manner in the nanomolar range. This peptide is highly selective for ATGL and does not inhibit other lipases including hormone sensitive lipase, monoacylglycerol lipase, lipoprotein lipase, and patatin-domain containing phospholipases 6 and 7. Since increased lipolysis is linked to the development of metabolic disorders the inhibition of ATGL by G0S2 derived peptides may represent a novel therapeutic tool to modulate lipolysis.