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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Pollak, NM; Schweiger, M; Jaeger, D; Kolb, D; Kumari, M; Schreiber, R; Kolleritsch, S; Markolin, P; Grabner, GF; Heier, C; Zierler, KA; Rülicke, T; Zimmermann, R; Lass, A; Zechner, R; Haemmerle, G.
Cardiac-specific overexpression of perilipin 5 provokes severe cardiac steatosis via the formation of a lipolytic barrier.
J Lipid Res. 2013; 54(4):1092-102 Doi: 10.1194/jlr.M034710 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Co-Autor*innen der Med Uni Graz
Grabner Gernot
Kolb Dagmar
Schreiber Renate
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Abstract:
Cardiac triacylglycerol (TG) catabolism critically depends on the TG hydrolytic activity of adipose triglyceride lipase (ATGL). Perilipin 5 (Plin5) is expressed in cardiac muscle (CM) and has been shown to interact with ATGL and its coactivator comparative gene identification-58 (CGI-58). Furthermore, ectopic Plin5 expression increases cellular TG content and Plin5-deficient mice exhibit reduced cardiac TG levels. In this study we show that mice with cardiac muscle-specific overexpression of perilipin 5 (CM-Plin5) massively accumulate TG in CM, which is accompanied by moderately reduced fatty acid (FA) oxidizing gene expression levels. Cardiac lipid droplet (LD) preparations from CM of CM-Plin5 mice showed reduced ATGL- and hormone-sensitive lipase-mediated TG mobilization implying that Plin5 overexpression restricts cardiac lipolysis via the formation of a lipolytic barrier. To test this hypothesis, we analyzed TG hydrolytic activities in preparations of Plin5-, ATGL-, and CGI-58-transfected cells. In vitro ATGL-mediated TG hydrolysis of an artificial micellar TG substrate was not inhibited by the presence of Plin5, whereas Plin5-coated LDs were resistant toward ATGL-mediated TG catabolism. These findings strongly suggest that Plin5 functions as a lipolytic barrier to protect the cardiac TG pool from uncontrolled TG mobilization and the excessive release of free FAs.
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1-Acylglycerol-3-Phosphate O-Acyltransferase - genetics, metabolism
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COS Cells - administration & dosage
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Energy Metabolism - genetics, physiology
Immunoblotting - administration & dosage
Intracellular Signaling Peptides and Proteins - genetics, metabolism
Lipase - genetics, metabolism
Lipolysis - genetics, physiology
Mice - administration & dosage
Mice, Transgenic - administration & dosage
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adipose triglyceride lipase
cardiac lipid
energy metabolism
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