Comparative gene identification-58/α/β hydrolase domain 5: more than just an adipose triglyceride lipase activator?

Comparative gene identification-58 (CGI-58) is a lipid droplet-associated protein that controls intracellular triglyceride levels by its ability to activate adipose triglyceride lipase (ATGL). Additionally, CGI-58 was described to exhibit lysophosphatidic acid acyl transferase (LPAAT) activity. This review focuses on the significance of CGI-58 in energy metabolism in adipose and nonadipose tissue.

Recent studies with transgenic and CGI-58-deficient mouse strains underscored the importance of CGI-58 as a regulator of intracellular energy homeostasis by modulating ATGL-driven triglyceride hydrolysis. In accordance with this function, mice and humans that lack CGI-58 accumulate triglyceride in multiple tissues. Additionally, CGI-58-deficient mice develop an ATGL-independent severe skin barrier defect and die soon after birth. Although the premature death prevented a phenotypical characterization of adult global CGI-58 knockout mice, the characterization of mice with tissue-specific CGI-58 deficiency revealed new insights into its role in neutral lipid and energy metabolism. Concerning the ATGL-independent function of CGI-58, a recently identified LPAAT activity for CGI-58 was shown to be involved in the generation of signaling molecules regulating inflammatory processes and insulin action.

Although the function of CGI-58 in the catabolism of cellular triglyceride depots via ATGL is well established, further studies are required to consolidate the function of CGI-58 as LPAAT and to clarify the involvement of CGI-58 in the metabolism of skin lipids.