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

The saturated fatty acid (SFA) palmitate induces insulin resistance in cultured skeletal muscle cells, which may be related to NF-kappaB 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 C(2)C(12) 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-kappaB 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-kappaB DNA binding activity in both L6 and C(2)C(12) cells, C16:0 also induced NF-kappaB transcriptional activity. C18:0 showed comparable effects, whereas the SFAs with shorter chain lengths were not able to elevate NF-kappaB transcriptional activity. Collectively, these results demonstrate that SFA-induced NF-kappaB activation coincides with insulin resistance and depends on FA chain length.