Linked Life Data

16204338

Source:http://linkedlifedata.com/resource/pubmed/id/16204338

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-1-11
pubmed:abstractText
Thyroid hormone regulates metabolism through transcriptional and posttranscriptional mechanisms. The integration of these mechanisms in heart is poorly understood. Therefore, we investigated control of substrate flux into the citric acid cycle (CAC) by thyroid hormone using retrogradely perfused isolated hearts (n = 20) from control (C) and age-matched thyroidectomized rats (T). We determined substrate flux and fractional contributions (Fc) to the CAC by 13C-NMR spectroscopy and isotopomer analyses in hearts perfused with [1,3-(13)C]acetoacetic acid (0.17 mM), L-[3-(13)C]lactic acid (LAC, 1.2 mM), [U-13C]long-chain mixed free fatty acids (FFA, 0.35 mM), and unlabeled glucose. Some T hearts were supplied triiodothyronine (T3, 10 nM; TT) for 60 min. Prolonged hypothyroid state reduced myocardial oxygen consumption, although T3 produced no significant change. Hypothyroidism reduced overall CAC(flux) but selectively altered only FFA(flux) among the individual substrates, though LAC(flux) trended upward. T3 rapidly decreased lactate Fc and flux. 13C labeling of glutamine through glutamate was increased in T with further enhancement in TT. The glutamate-to-glutamine ratio was significantly lower in T and TT. Immunoblots detected a decrease in hypothyroid hearts for muscle carnitine palmitoyltransferase I (CPT I) and a marked increase in pyruvate dehydrogenase kinase (PDK)-2 with no changes in liver CPT I, PDK-4, or hexokinase 2. TT, but not T, displayed elevated glutamine synthetase (GS) expression. These studies showed that T3 regulates cardiac metabolism through integration of several mechanisms, including changes in oxidative enzyme content and rapid modulation of individual substrates fluxes. T3 also moderates forward glutamine flux, possibly by increasing the overall activity of GS.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0193-1849
pubmed:author
pubmed:issnType
Print
pubmed:volume
290
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
E372-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Thyroid hormone controls myocardial substrate metabolism through nuclear receptor-mediated and rapid posttranscriptional mechanisms.
pubmed:affiliation
Division of Cardiology, Department of Pediatrics, University of Washington, Seattle, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural