CGI-58’S ABILITY TO REGULATE HEPATIC TRIACYLGLYCEROL METABOLISM DOES NOT REQUIRE ATGL CO-ACTIVATION

Adipose Triglyceride Lipase (ATGL) and Comparative Gene Identification 58 (CGI-58) are critical regulators of triacylglycerol (TAG) turnover. CGI-58 is thought to regulate TAG mobilization by stimulating the enzymatic activity of ATGL. However, it is not known whether this coactivation function of C...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Cell reports (Cambridge) 2016-07, Vol.16 (4), p.939-949
Hauptverfasser: Lord, Caleb C., Ferguson, Daniel, Thomas, Gwynneth, Brown, Amanda L., Schugar, Rebecca C., Burrows, Amy, Gromovsky, Anthony D., Betters, Jenna, Neumann, Chase, Sacks, Jessica, Marshall, Stephanie, Watts, Russell, Schweiger, Martina, Lee, Richard G., Crooke, Rosanne M., Graham, Mark J., Lathia, Justin D., Sakaguchi, Takuya F., Lehner, Richard, Haemmerle, Guenter, Zechner, Rudolf, Brown, J. Mark
Format: Artikel
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Adipose Triglyceride Lipase (ATGL) and Comparative Gene Identification 58 (CGI-58) are critical regulators of triacylglycerol (TAG) turnover. CGI-58 is thought to regulate TAG mobilization by stimulating the enzymatic activity of ATGL. However, it is not known whether this coactivation function of CGI-58 occurs in vivo. Moreover, the phenotype of human CGI-58 mutations suggests ATGL-independent functions. Through direct comparison of mice with single or double deficiency of CGI-58 and ATGL, we show here that CGI-58 knockdown causes hepatic steatosis in both the presence and absence of ATGL. CGI-58 also regulates hepatic diacylglycerol (DAG) and inflammation in an ATGL-independent manner. Interestingly, ATGL deficiency, but not CGI-58 deficiency, results in suppression of the hepatic and adipose de novo lipogenic program. Collectively, these findings show that CGI-58 regulates hepatic neutral lipid storage and inflammation in the genetic absence of ATGL, demonstrating that mechanisms driving TAG lipolysis in hepatocytes differ significantly from those in adipocytes. Comparative Gene Identification 58 (CGI-58) is thought to regulate triacylglycerol mobilization by stimulating the enzymatic activity of Adipose Triglyceride Lipase (ATGL). Lord et al. now show that CGI-58 regulates hepatic triacylglycerol turnover and inflammation in the genetic absence of ATGL, demonstrating an ATGL-independent role for CGI-58 in mouse liver.
ISSN:2211-1247
DOI:10.1016/j.celrep.2016.06.049