Palmitate-induced skeletal muscle insulin resistance does not require NF-κB activation

P.P. Hommelberg, J. Plat, L.M. Sparks, A.M.W.J. Schols, A.L. van Essen, M.C. Kelders, D. Van Beurden, R.P. Mensink, R.C.J. Langen

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Abstract

Palmitate activates the NF-kappaB pathway, and induces accumulation of lipid metabolites and insulin resistance in skeletal muscle cells. Little information is available whether and how these processes are causally related. Therefore, the objectives were to investigate whether intra-cellular lipid metabolites are involved in FA-induced NF-kappaB activation and/or insulin resistance in skeletal muscle and to investigate whether FA-induced insulin resistance and NF-kappaB activation are causally related. Inhibiting DGAT or CPT-1 by using, respectively, amidepsine or etomoxir increased DAG accumulation and sensitized myotubes to palmitate-induced insulin resistance. While co-incubation of palmitate with etomoxir increased NF-kappaB transactivation, co-incubation with amidepsine did not, indicating that DAG accumulation is associated with insulin resistance but not with NF-kappaB activation. Furthermore, pharmacological or genetic inhibition of the NF-kappaB pathway could not prevent palmitate-induced insulin resistance. In conclusion, we have demonstrated that activation of the NF-kappaB pathway is not required for palmitate-induced insulin resistance in skeletal muscle cells.
Original languageEnglish
Pages (from-to)1215-1225
Number of pages11
JournalCellular and Molecular Life Sciences
Volume68
Issue number7
DOIs
Publication statusPublished - Apr 2011

Keywords

  • Skeletal muscle
  • Insulin resistance
  • Palmitate
  • Nuclear factor-kappa B
  • Glucose uptake
  • PROTEIN-KINASE-C
  • SATURATED FATTY-ACIDS
  • RECEPTOR SUBSTRATE-1
  • DIACYLGLYCEROL ACYLTRANSFERASE
  • SERINE PHOSPHORYLATION
  • NUCLEAR-LOCALIZATION
  • GLUCOSE-UPTAKE
  • SINGLE BOUT
  • ACYL-COA
  • INHIBITION

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