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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2004-3-1
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pubmed:abstractText |
Lipid infusion or ingestion of a high-fat diet results in insulin resistance, but the mechanism underlying this phenomenon remains unclear. Here we show that, in rats fed a high-fat diet, whole-animal, muscle and liver insulin resistance is ameliorated following hepatic overexpression of malonyl-coenzyme A (CoA) decarboxylase (MCD), an enzyme that affects lipid partitioning. MCD overexpression decreased circulating free fatty acid (FFA) and liver triglyceride content. In skeletal muscle, levels of triglyceride and long-chain acyl-CoA (LC-CoA)-two candidate mediators of insulin resistance-were either increased or unchanged. Metabolic profiling of 36 acylcarnitine species by tandem mass spectrometry revealed a unique decrease in the concentration of one lipid-derived metabolite, beta-OH-butyrate, in muscle of MCD-overexpressing animals. The best explanation for our findings is that hepatic expression of MCD lowered circulating FFA levels, which led to lowering of muscle beta-OH-butyrate levels and improvement of insulin sensitivity.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1078-8956
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
268-74
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:14770177-Acyl Coenzyme A,
pubmed-meshheading:14770177-Adenoviridae,
pubmed-meshheading:14770177-Animals,
pubmed-meshheading:14770177-Carboxy-Lyases,
pubmed-meshheading:14770177-Carnitine,
pubmed-meshheading:14770177-Cells, Cultured,
pubmed-meshheading:14770177-Dietary Fats,
pubmed-meshheading:14770177-Hepatocytes,
pubmed-meshheading:14770177-Insulin,
pubmed-meshheading:14770177-Insulin Resistance,
pubmed-meshheading:14770177-Lipid Metabolism,
pubmed-meshheading:14770177-Liver,
pubmed-meshheading:14770177-Male,
pubmed-meshheading:14770177-Muscle, Skeletal,
pubmed-meshheading:14770177-Rats,
pubmed-meshheading:14770177-Rats, Wistar,
pubmed-meshheading:14770177-Triglycerides
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pubmed:year |
2004
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pubmed:articleTitle |
Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance.
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pubmed:affiliation |
Sarah W. Stedman Nutrition and Metabolism Center and Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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