Linked Life Data

21545834

Source:http://linkedlifedata.com/resource/pubmed/id/21545834

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-6-20
pubmed:abstractText
Obesity due to nutrient excess leads to chronic pathologies including type 2 diabetes and cardiovascular disease. Related to nutrient excess, FoxO1 has a role in regulating fatty acid uptake and oxidation and triglyceride (TG) storage by mechanisms that are largely unresolved. We examined the mechanism behind palmitate (PA)-induced TG accumulation in cardiomyocytes. To mimic lipid excess, rat ventricular myocytes were incubated with albumin-bound PA (1 mM) or rats were administered Intralipid (20%). PA-treated cardiomyocytes showed a substantial increase in TG accumulation, accompanied by amplification of nuclear migration of phospho-p38 and FoxO1, iNOS induction, and translocation of CD36 to the plasma membrane. PA also increased Cdc42 protein and its tyrosine nitration, thereby rearranging the cytoskeleton and facilitating CD36 translocation. These effects were duplicated by TNF-? and reversed by the iNOS inhibitor 1400 W. PA increased the nuclear interaction between FoxO1 and NF-?B, reduced the nuclear presence of PGC-1?, and downregulated expression of oxidative phosphorylation proteins. In vivo a robust increase in cardiac TGs after Intralipid administration was also associated with augmentation of nuclear FoxO1 and iNOS expression. Impeding this FoxO1-iNOS-CD36 pathway could decrease cardiac lipid accumulation and oxidative/nitrosative stress and help ameliorate the cardiovascular complications associated with obesity and diabetes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1873-4596
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
352-63
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Cardiac triglyceride accumulation following acute lipid excess occurs through activation of a FoxO1-iNOS-CD36 pathway.
pubmed:affiliation
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't