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This Article Full Text Full Text (PDF) All Versions of this Article: 296/1/E114    most recent 00436.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hommelberg, P. P. H. Articles by Mensink, R. P. Search for Related Content PubMed PubMed Citation Articles by Hommelberg, P. P. H. Articles by Mensink, R. P.

Fatty acid-induced NF-B activation and insulin resistance in skeletal muscle are chain length dependent

¹Department of Human Biology and ²Department of Respiratory Medicine, Maastricht University, Maastricht; and ³Top Institute of Food and Nutrition, Wageningen, The Netherlands

Submitted 6 July 2007 ; accepted in final form 24 October 2008

The saturated fatty acid (SFA) palmitate induces insulin resistance in cultured skeletal muscle cells, which may be related to NF-B activation. The aim of this study was to evaluate whether other SFAs also exert these effects on skeletal muscle and whether these relate to chain length. Therefore, we incubated L6 and C₂C₁₂ skeletal muscle cells with four different fatty acids, caprylate (C8:0), laurate (C12:0), palmitate (C16:0), and stearate (C18:0), to study effects on GLUT4 translocation, deoxyglucose uptake, and NF-B activation. Incubation of L6 cells with the long-chain FAs C16:0 and C18:0 reduced insulin-stimulated GLUT4 translocation and deoxyglucose uptake, whereas L6 cells incubated with the medium-chain FAs C8:0 and C12:0 remained insulin sensitive. Besides increasing NF-B DNA binding activity in both L6 and C₂C₁₂ cells, C16:0 also induced NF-B transcriptional activity. C18:0 showed comparable effects, whereas the SFAs with shorter chain lengths were not able to elevate NF-B transcriptional activity. Collectively, these results demonstrate that SFA-induced NF-B activation coincides with insulin resistance and depends on FA chain length.

glucose transporter 4 translocation; nuclear factor-B activation; fatty acid chain length

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