Unsaturated fatty acids block the effects of saturated fatty acids on insulin signaling in astrocytoma cells

Abstract

Objective: Obesity is associated with an increased risk of many diseases. Plasma concentrations of fatty acids are significantly increased in obese and metabolic syndrome patients, and saturated fatty acids (SFAs) can activate inflammatory responses in the periphery and neurons and are also associated with insulin resistance. However, their effects on astrocyte and their role in energy homeostasis of CNS have not been clearly evaluated. To find out the effects of SFA on astrocyte and energy metabolism, we investigated the effects of SFA on insulin signaling and associated pathways in the U87 astrocytoma cell line. Also, we investigated how the unsaturated fatty acids (UFAs) affected the effects of the SFA.Methods and Results: We used the human astrocytoma cell line U87MG treated with SFAs (palmitate, stearate) and UFAs (oleic acid, linoleic acid). The exposure to SFAs attenuated insulin signaling in U87 MG cells, which was revealed by the Akt phosphorylation. SFAs induced IL-6, and IL-8 mRNA expression, but did not affect IL-1β and TNF–α mRNA expression. SFAs induced ER stress, which assessed by Xbp-1 splicing and CHOP mRNA expression, however, did not induce apoptosis. SFA also activated JNK dependent pathway. These changes were reversed by treatments of UFAs. Conclusions: SFAs attenuated the insulin signaling, induced the inflammatory cytokines, and generated ER stress in astrocytoma cells. UFAs reversed the effects of SFAs, which showed that UFAs rich diet can be a useful candidate for attenuating the effects of SFAs in astrocytes.