Palmitate-induced skeletal muscle insulin resistance does not require NF-κB activation |
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Authors: | Pascal P H Hommelberg Jogchum Plat Lauren M Sparks Annemie M W J Schols Anon L M van Essen Marco C J M Kelders Denis van Beurden Ronald P Mensink Ramon C J Langen |
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Institution: | (1) Department of Human Biology, Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands;(2) Department of Respiratory Medicine, Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, P.O. Box 616, 6200 MD Maastricht, The Netherlands;(3) Top Institute Food and Nutrition, Wageningen, The Netherlands; |
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Abstract: | Palmitate activates the NF-κB 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-κB activation and/or insulin resistance
in skeletal muscle and to investigate whether FA-induced insulin resistance and NF-κB 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-κB transactivation, co-incubation with amidepsine
did not, indicating that DAG accumulation is associated with insulin resistance but not with NF-κB activation. Furthermore,
pharmacological or genetic inhibition of the NF-κB pathway could not prevent palmitate-induced insulin resistance. In conclusion,
we have demonstrated that activation of the NF-κB pathway is not required for palmitate-induced insulin resistance in skeletal
muscle cells. |
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