Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Zierler, KA; Jaeger, D; Pollak, NM; Eder, S; Rechberger, GN; Radner, FP; Woelkart, G; Kolb, D; Schmidt, A; Kumari, M; Preiss-Landl, K; Pieske, B; Mayer, B; Zimmermann, R; Lass, A; Zechner, R; Haemmerle, G.
Functional cardiac lipolysis in mice critically depends on comparative gene identification-58.
J Biol Chem. 2013; 288(14):9892-9904
Doi: 10.1074/jbc.M112.420620
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- Co-Autor*innen der Med Uni Graz
- Kolb Dagmar
- Pieske Burkert Mathias
- Schmidt Albrecht
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- 1-Acylglycerol-3-Phosphate O-Acyltransferase - metabolism
- Adipose Tissue - enzymology
- Animals -
- Cardiomyopathies - metabolism
- Echocardiography - methods
- Female -
- Glucose - metabolism
- Homeostasis -
- Hydrolysis -
- Lipase - metabolism
- Lipid Metabolism -
- Lipids - chemistry
- Lipolysis - physiology
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- Mice -
- Mitochondria - metabolism
- Muscles - enzymology Muscles - metabolism
- Myocardium - metabolism
- Oxygen Consumption -
- Triglycerides - metabolism