Cardiomyocyte-specific perilipin 5 overexpression leads to myocardial steatosis and modest cardiac dysfunction.
Presence of ectopic lipid droplets (LDs) in cardiac muscle is associated to lipotoxicity and tissue dysfunction. However, presence of LDs in heart is also observed in physiological conditions, such as when cellular energy needs and energy production from mitochondria fatty acid β-oxidation are high (fasting). This suggests that development of tissue lipotoxicity and dysfunction is not simply due to the presence of LDs in cardiac muscle but due at least in part to alterations in LD function. To examine the function of cardiac LDs, we obtained transgenic mice with heart-specific perilipin 5 (Plin5) overexpression (MHC-Plin5), a member of the perilipin protein family. Hearts from MHC-Plin5 mice expressed at least 4-fold higher levels of plin5 and exhibited a 3.5-fold increase in triglyceride content versus nontransgenic littermates. Chronic cardiac excess of LDs was found to result in mild heart dysfunction with decreased expression of peroxisome proliferator-activated receptor (PPAR)α target genes, decreased mitochondria function, and left ventricular concentric hypertrophia. Lack of more severe heart function complications may have been prevented by a strong increased expression of oxidative-induced genes via NF-E2-related factor 2 antioxidative pathway. Perilipin 5 regulates the formation and stabilization of cardiac LDs, and it promotes cardiac steatosis without major heart function impairment.
Department of Medicine, School of Medicine, University of Maryland, Baltimore, MD, USA.
Hong
H
Wang
Urmila
U
Sreenivasan
Da-Wei
DW
Gong
Kelly A
KA
O'Connell
Erinne R
ER
Dabkowski
Peter A
PA
Hecker
Nicoleta
N
Ionica
Manige
M
Konig
Anup
A
Mahurkar
Yezhou
Y
Sun
William C
WC
Stanley
Carole
C
Sztalryd
D000818:Animals; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D004272:DNA, Mitochondrial / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D000070797:Perilipin-5; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D004272:DNA, Mitochondrial; D000070797:Perilipin-5; C511805:Plin5 protein, mouse; D011506:Proteins; D017382:Reactive Oxygen Species; D014280:Triglycerides