A peptide derived from G0/G1 switch gene 2 acts as noncompetitive inhibitor of adipose triglyceride lipase

J Biol Chem. 2014 Nov 21;289(47):32559-70. doi: 10.1074/jbc.M114.602599. Epub 2014 Sep 25.


The protein G0/G1 switch gene 2 (G0S2) is a small basic protein that functions as an endogenous inhibitor of adipose triglyceride lipase (ATGL), a key enzyme in intracellular lipolysis. In this study, we identified a short sequence covering residues Lys-20 to Ala-52 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 noncompetitive 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. Because 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.

Keywords: Adipose Triglyceride Lipase (ATGL); Atglistatin; Enzyme Inhibitor; G0/G1 Switch Gene 2 (G0S2); Lipid; Lipid Metabolism; Lipolysis; Noncompetitive Inhibition; Peptides; hGW2052.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Acylglycerol-3-Phosphate O-Acyltransferase / antagonists & inhibitors
  • 1-Acylglycerol-3-Phosphate O-Acyltransferase / genetics
  • 1-Acylglycerol-3-Phosphate O-Acyltransferase / metabolism
  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chlorocebus aethiops
  • Dose-Response Relationship, Drug
  • Humans
  • Lipase / antagonists & inhibitors*
  • Lipase / genetics
  • Lipase / metabolism
  • Mice, Knockout
  • Molecular Sequence Data
  • Peptides / genetics
  • Peptides / pharmacology*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism*


  • Cell Cycle Proteins
  • G0S2 protein, human
  • Peptides
  • Recombinant Proteins
  • 1-Acylglycerol-3-Phosphate O-Acyltransferase
  • Abhd5 protein, mouse
  • Lipase
  • PNPLA2 protein, human
  • PNPLA2 protein, mouse