cis-9,trans-11-Conjugated linoleic acid activates AMP-activated protein kinase in attenuation of insulin resistance in C2C12 myotubes.

Obesity is a key risk factor in the development of insulin resistance (IR). This study is to investigate the IR attenuating effect and the molecular mechanism of cis-9,trans-11-conjugated linoleic acid (c9,t11-CLA). This study was performed with a palmitate-induced IR model using C(2)C(12) myotubes and showed that c9,t11-CLA increased insulin-stimulated and basal (non-insulin-stimulated) glucose uptake of IR myotubes. c9,t11-CLA also up-regulated the levels of phosphorglycogen synthase, phosphoracetyl CoA carboxylase, and carnitine palmitoyltransferase-1 while down-regulating the level of pyruvate dehydrogenase kinase 4 under insulin-stimulated and basal conditions. However, c9,t11-CLA did not affect protein kinase B/Akt (Akt). These results suggested that c9,t11-CLA induced an insulin-independent enhancement of glucose and fatty acid metabolism. Furthermore, there was a dose- and time-dependent increase in the expression of phosphor-AMP-activated protein kinase (AMPK), whereas LKB1, the upstream kinase of AMPK, was unchanged. Collectively, c9,t11-CLA attenuated palmitate-induced IR by increasing the consumption of glucose and fatty acid, the mechanism involving the direct activation of AMPK.