Effects of a brief high-fat diet and acute exercise on the mTORC1 and IKK/NF-kB pathways in rat skeletal muscle

One exercise session can improve subsequent insulin-stimulated glucose uptake by skeletal muscle in healthy and insulin-resistant individuals. Our first aim was to determine whether a brief (2 weeks) high-fat diet (HFD) that caused muscle insulin resistance would activate the mammalian target of rapamycin complex 1 (mTORC1) and/or inhibitor of  kB kinase/nuclear factor  B (IKK/NF-kB) pathways, which are potentially linked to induction of insulin resistance. Our second aim was to determine whether acute exercise that improved insulin-stimulated glucose uptake by muscles would attenuate activation of these pathways. We compared HFD-fed rats with rats fed a low-fat diet (LFD). Some animals from each diet group were sedentary and others were studied 3 h postexercise, when insulin-stimulated glucose uptake was increased. The results did not provide evidence that brief HFD activated either the mTORC1 (including phosphorylation of mTOR^Ser2448, TSC2^Ser939, p70S6K^Thr412, and RPS6^Ser235/236) or the IKK/NF- kB (including abundance of I B  or phosphorylation of NF-kB^Ser536, IKKa / b^Ser177/181, and IkB^Ser32) pathway in insulin-resistant muscles. Exercise did not oppose the activation of either pathway, as evidenced by no attenuation of phosphorylation of key proteins in the IKK/NF- B pathway (NF-kB^Ser536, IKKa/bSer177/181, and IkB^Ser32), unaltered I B  abundance, and no attenuation of phosphorylation of key proteins in the mTORC1 pathway (mTOR^Ser2448, TSC2^Ser939, and RPS6^Ser235/236). Instead, exercise induced greater phosphorylation of 2 proteins of the mTORC1 pathway (PRA^S40Thr246 and p70S6K^Thr412) in insulinstimulated muscles, regardless of diet. Insulin resistance induced by a brief HFD was not attributable to greater activation of the mTORC1 or the IKK/NF- kB pathway in muscle, and exercise-induced improvement in insulin sensitivity was not attributable to attenuated activation of these pathways in muscle.