Linked Life Data

18042664

Source:http://linkedlifedata.com/resource/pubmed/id/18042664

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-2-8
pubmed:abstractText
Stearoyl-CoA desaturase (SCD) is a lipogenic enzyme that catalyzes the synthesis of monounsaturated fatty acids (FA). SCD1 deficiency activates metabolic pathways that promote FA beta-oxidation and decrease lipogenesis in liver. In the present study, we show that FA transport and oxidation are decreased, whereas glucose uptake and oxidation are increased in the heart of SCD1(-/-) mice. Protein levels of FA transport proteins such as FA translocase/CD36 and FA transport protein as well as activity of carnitine palmitoyltransferase 1, the rate-limiting enzyme for mitochondrial fat oxidation, were significantly lower in the heart of SCD1(-/-) mice compared with SCD1(+/+) mice. Consequently, the rate of palmitoyl-CoA oxidation was decreased significantly in the heart of SCD1(-/-) mice. mRNA levels of peroxisome proliferator-activated receptor-alpha, a key transcription factor controlling genes of FA oxidation, were significantly reduced in SCD1(-/-) mice. Phosphorylation of insulin receptor substrate-1 (IRS-1) and the association of alphap85 subunit of phosphatidylinositol 3-kinase with IRS-1 were significantly higher under both basal and insulin-stimulated conditions in SCD1(-/-) hearts. This increased insulin sensitivity translated to a 1.8-fold greater 2-deoxyglucose uptake and 2-fold higher rate of glucose oxidation in the myocardium compared with SCD1(+/+) counterparts. The results suggest that SCD1 deficiency causes a shift in cardiac substrate utilization from FA to glucose by upregulating insulin signaling, decreasing FA availability, and reducing expression of FA oxidation genes in the heart. This increase in cardiac insulin sensitivity and glucose utilization due to SCD1 deficiency could prove therapeutic in pathological conditions such as obesity that are characterized by skewed cardiac substrate utilization.
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
294
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
E357-64
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:18042664-Animals, pubmed-meshheading:18042664-Blotting, Western, pubmed-meshheading:18042664-Carnitine O-Palmitoyltransferase, pubmed-meshheading:18042664-Echocardiography, pubmed-meshheading:18042664-Fatty Acids, pubmed-meshheading:18042664-Glucose, pubmed-meshheading:18042664-Heart, pubmed-meshheading:18042664-Insulin, pubmed-meshheading:18042664-Lipid Metabolism, pubmed-meshheading:18042664-Male, pubmed-meshheading:18042664-Mice, pubmed-meshheading:18042664-Mice, Knockout, pubmed-meshheading:18042664-Microsomes, pubmed-meshheading:18042664-Myocardium, pubmed-meshheading:18042664-Oxidation-Reduction, pubmed-meshheading:18042664-PPAR alpha, pubmed-meshheading:18042664-Palmitates, pubmed-meshheading:18042664-RNA, pubmed-meshheading:18042664-Signal Transduction, pubmed-meshheading:18042664-Stearoyl-CoA Desaturase
pubmed:year
2008
pubmed:articleTitle
Loss of stearoyl-CoA desaturase 1 inhibits fatty acid oxidation and increases glucose utilization in the heart.
pubmed:affiliation
Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural