Journal article
Functional cardiac lipolysis in mice critically depends on comparative gene identification-58
Journal of Biological Chemistry, Vol.288(14), pp.9892-9904
2013
Abstract
Efficient catabolism of cellular triacylglycerol (TG) stores requires the TG hydrolytic activity of adipose triglyceride lipase (ATGL). The presence of comparative gene identification-58 (CGI-58) strongly increased ATGL-mediated TG catabolism in cell culture experiments. Mutations in the genes coding for ATGL or CGI-58 in humans cause neutral lipid storage disease characterized by TG accumulation in multiple tissues. ATGL gene mutations cause a severe phenotype especially in cardiac muscle leading to cardiomyopathy that can be lethal. In contrast, CGI-58 gene mutations provoke severe ichthyosis and hepatosteatosis in humans and mice, whereas the role of CGI-58 in muscle energy metabolism is less understood. Here we show that mice lacking CGI-58 exclusively in muscle (CGI-58KOM) developed severe cardiac steatosis and cardiomyopathy linked to impaired TG catabolism and mitochondrial fatty acid oxidation. The marked increase in ATGL protein levels in cardiac muscle of CGI-58KOM mice was unable to compensate the lack of CGI-58. The addition of recombinant CGI-58 to cardiac lysates of CGI-58KOM mice completely reconstituted TG hydrolytic activities. In skeletal muscle, the lack of CGI-58 similarly provoked TG accumulation. The addition of recombinant CGI-58 increased TG hydrolytic activities in control and CGI-58KOM tissue lysates, elucidating the limiting role of CGI-58 in skeletal muscle TG catabolism. Finally, muscle CGI-58 deficiency affected whole body energy homeostasis, which is caused by impaired muscle TG catabolism and increased cardiac glucose uptake. In summary, this study demonstrates that functional muscle lipolysis depends on both CGI-58 and ATGL. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
Details
- Title
- Functional cardiac lipolysis in mice critically depends on comparative gene identification-58
- Authors
- K A Zierler (Author) - University of Graz, AustriaD Jaeger (Author) - University of Graz, AustriaNina M Pollak (Author) - University of Graz, AustriaS Eder (Author) - University of Graz, AustriaG N Rechberger (Author) - University of Graz, AustriaF P W Radner (Author) - University of Graz, AustriaG Woelkart (Author) - University of Graz, AustriaD Kolb (Author) - University of Graz, AustriaA Schmidt (Author) - Medical University of Graz, AustriaM Kumari (Author) - University of Graz, AustriaK Preiss-Landl (Author) - University of Graz, AustriaB Pieske (Author) - University of Graz, AustriaB Mayer (Author) - University of Graz, AustriaR Zimmermann (Author) - University of Graz, AustriaA Lass (Author) - University of Graz, AustriaR Zechner (Author) - University of Graz, AustriaG Haemmerle (Author) - University of Graz, Austria
- Publication details
- Journal of Biological Chemistry, Vol.288(14), pp.9892-9904
- Publisher
- American Society for Biochemistry and Molecular Biology, Inc.
- Date published
- 2013
- DOI
- 10.1074/jbc.M112.420620
- ISSN
- 0021-9258
- Copyright note
- Copyright © 2013 by the American Society for Biochemistry and Molecular Biology, Inc. The published version is reproduced here in accordance with the publisher's copyright policy.
- Organisation Unit
- School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99451205702621
- Output Type
- Journal article
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