Palmitic acid causes insulin resistance in granulosa cells via activation of JNK.

Obesity is a worldwide health problem with rising incidence and results in reproductive difficulties. Elevated saturated free fatty acids (FFAs) in obesity can cause insulin resistance (IR) in peripheral tissues. The high intra-follicular saturated FFAs may also account for IR in ovarian granulosa cells (GCs). In the present study, we investigated the relationship between saturated FFAs and IR in GCs by the use of palmitic acid (PA). We demonstrated that the glucose uptake in cultured GCs and lactate accumulation in the culture medium were stimulated by insulin, but the effects of insulin were attenuated by PA treatment. Besides, insulin-induced phosphorylation of Akt was reduced by PA in a dose and time-dependent manner. Furthermore, PA increased phosphorylation of JNK and JNK blockage rescued the phosphorylation of Akt which was down-regulated by PA. These findings highlighted the negative effect of PA on GCs metabolism and may partially account for the obesity-related reproductive disorders.