Palmitate-induced skeletal muscle insulin resistance does not require NF-κB activation.
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.
Hommelberg
Pascal P H
PP
Department of Human Biology, Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
Plat
Jogchum
J
Sparks
Lauren M
LM
Schols
Annemie M W J
AM
van Essen
Anon L M
AL
Kelders
Marco C J M
MC
van Beurden
Denis
D
Mensink
Ronald P
RP
Langen
Ramon C J
RC
D000818:Animals; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology; D004075:Diglycerides / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism / Q000494:pharmacology*
D004075:Diglycerides; D005230:Fatty Acids, Nonesterified; D016328:NF-kappa B; D010168:Palmitates
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