Regulation of Hepatic Triacylglycerol Metabolism by CGI-58 Does Not Require ATGL Co-activation.
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| Abstract |
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.
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| Authors | Caleb C Lord, Daniel Ferguson, Gwynneth Thomas, Amanda L Brown, Rebecca C Schugar, Amy Burrows, Anthony D Gromovsky, Jenna Betters, Chase Neumann, Jessica Sacks, Stephanie Marshall, Russell Watts, Martina Schweiger, Richard G Lee, Rosanne M Crooke, Mark J Graham, Justin D Lathia, Takuya F Sakaguchi, Richard Lehner, Guenter Haemmerle, Rudolf Zechner, J Mark Brown |
| Journal | Cell reports (Cell Rep) Vol. 16 Issue 4 Pg. 939-949 (07 26 2016) ISSN: 2211-1247 [Electronic] United States |
| PMID | 27396333 (Publication Type: Journal Article) |
| Copyright | Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved. |
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