Muscle Cell Palmitate-Induced Insulin Resistance, JNK, IKK/NF-κB and STAT3 Activation are Attenuated by Carnosic and Rosmarinic Acid.

Abstract

The worldwide epidemic of obesity has drastically worsened with the increase in more sedentary lifestyles and increased consumption of fatty foods. Increased blood free fatty acids (FFAs), often observed in obesity, leads to impaired insulin action, and promotes the development of insulin resistance and Type 2 diabetes mellitus (T2DM). JNK, IKK-NF-κB, and STAT3 are known to be involved in skeletal muscle insulin resistance. We reported previously that carnosic acid (CA) and rosmarinic acid (RA), attenuated the palmitate-induced skeletal muscle insulin resistance, an effect that was associated with increased AMPK activation and reduced mTOR-p70S6K signaling. In the present study, we examined the effects of CA and RA on JNK, IKK-NF-κB, and STAT3. Exposure of cells to palmitate increased the phosphorylation/activation of JNK, IKKα/β, IκBα, NF-κBp65, and STAT3. Importantly, CA and RA attenuated the deleterious effects of palmitate. Our data indicate that CA and RA have the potential to counteract the palmitate-induced skeletal muscle cell insulin resistance by modulating JNK, IKK-NF-κB, and STAT3 signaling.