Linked Life Data

20852389

Source:http://linkedlifedata.com/resource/pubmed/id/20852389

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2010-10-5
pubmed:abstractText
Excess lipid accumulation in the heart is associated with decreased cardiac function in humans and in animal models. The reasons are unclear, but this is generally believed to result from either toxic effects of intracellular lipids or excessive fatty acid oxidation (FAO). PPAR? expression is increased in the hearts of humans with metabolic syndrome, and use of PPAR? agonists is associated with heart failure. Here, mice with dilated cardiomyopathy due to cardiomyocyte PPAR? overexpression were crossed with PPAR?-deficient mice. Surprisingly, this cross led to enhanced expression of several PPAR-regulated genes that mediate fatty acid (FA) uptake/oxidation and triacylglycerol (TAG) synthesis. Although FA oxidation and TAG droplet size were increased, heart function was preserved and survival improved. There was no marked decrease in cardiac levels of triglyceride or the potentially toxic lipids diacylglycerol (DAG) and ceramide. However, long-chain FA coenzyme A (LCCoA) levels were increased, and acylcarnitine content was decreased. Activation of PKC? and PKC?, apoptosis, ROS levels, and evidence of endoplasmic reticulum stress were also reduced. Thus, partitioning of lipid to storage and oxidation can reverse cardiolipotoxicity despite increased DAG and ceramide levels, suggesting a role for other toxic intermediates such as acylcarnitines in the toxic effects of lipid accumulation in the heart.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1558-8238
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
120
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3443-54
pubmed:dateRevised
2011-3-30
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
PPAR?-induced cardiolipotoxicity in mice is ameliorated by PPAR? deficiency despite increases in fatty acid oxidation.
pubmed:affiliation
Division of Preventive Medicine and Nutrition, Columbia University, New York, New York 10032, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural