Effect of elevated lipid concentrations on human skeletal muscle gene expression

Tunstall, Rebecca and Cameron-Smith, David 2005, Effect of elevated lipid concentrations on human skeletal muscle gene expression, Metabolism, vol. 54, no. 7, pp. 952-959, doi: 10.1016/j.metabol.2005.02.012.

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Title Effect of elevated lipid concentrations on human skeletal muscle gene expression
Author(s) Tunstall, Rebecca
Cameron-Smith, David
Journal name Metabolism
Volume number 54
Issue number 7
Start page 952
End page 959
Publisher W.B. Saunders Co
Place of publication Duluth, Minn.
Publication date 2005-07
ISSN 0026-0495
Summary Dietary fatty acids regulate the abundance and activity of various proteins involved in the regulation of fat oxidation by functioning as regulators of gene transcription. To determine whether the transcription of key lipid metabolic proteins necessary for fat metabolism within human skeletal muscle are regulated by acute elevations in circulating free fatty acid (FFA) concentrations, 7 healthy men underwent 3 randomized resting infusions of Intralipid (20%) with heparin sodium, saline and heparin sodium, or saline only for 5 hours. These infusions significantly elevated plasma FFA concentrations by 15-fold (to 1.67 ± 0.13 mmol/L) in the Intralipid infusion trial, with modest elevations observed in the saline and heparin sodium and saline alone infusion groups (0.67 ± 0.09 and 0.49 ± 0.087 mmol/L, P < .01 both vs Intralipid infusion). Analysis of messenger RNA (mRNA) concentration demonstrated that pyruvate dehydrogenase kinase isoform 4 (PDK4) mRNA, a key negative regulator of glucose oxidation, was increased in all trials with a 24-fold response after Intralipid infusion, 15-fold after saline and heparin infusion, and 9-fold after saline alone. The PDK4 increases were not significantly different between the 3 trials. The mRNA concentration of the major uncoupling protein within skeletal muscle, uncoupling protein 3, was not elevated in parallel to the increased plasma FFA as similar (not, vert, similar2-fold) increases were evident in all trials. Additional genes involved in lipid transport (fatty acid translocase/CD36), oxidation (carnitine palmitoyltransferase I), and metabolism (1-acylglycerol-3-phosphate O-acyltransferase 1, hormone-sensitive lipase, and peroxisomal proliferator-activated receptor-γ coactivator-1α) were not altered by increased circulating FFA concentrations. The present data demonstrate that of the genes analyzed that encode proteins that are key regulators of lipid homeostasis within skeletal muscle, only the PDK4 gene is uniquely sensitive to increasing FFA concentrations after increased plasma FFA achieved by intravenous lipid infusion.
Language eng
DOI 10.1016/j.metabol.2005.02.012
Field of Research 111601 Cell Physiology
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2005, Elsevier Inc
Persistent URL http://hdl.handle.net/10536/DRO/DU:30003243

Document type: Journal Article
Collections: Faculty of Health
School of Health and Social Development
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