Cardiac-specific overexpression of perilipin 5 provokes severe cardiac steatosis via the formation of a lipolytic barrier.
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.
Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
Nina M
NM
Pollak
Martina
M
Schweiger
Doris
D
Jaeger
Dagmar
D
Kolb
Manju
M
Kumari
Renate
R
Schreiber
Stephanie
S
Kolleritsch
Philipp
P
Markolin
Gernot F
GF
Grabner
Christoph
C
Heier
Kathrin A
KA
Zierler
Thomas
T
Rülicke
Robert
R
Zimmermann
Achim
A
Lass
Rudolf
R
Zechner
Guenter
G
Haemmerle
D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D008066:Lipolysis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D014280:Triglycerides / Q000378:metabolism; D000217:Acyltransferases
D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D047908:Intracellular Signaling Peptides and Proteins; D008049:Lipase; D009124:Muscle Proteins; D014280:Triglycerides; C551268:lipid storage droplet protein 5, mouse; C492986:Abhd5 protein, mouse; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases