The effect of high fat diet and saturated fatty acids on insulin signaling in the amygdala and hypothalamus of rats.

Insulin injections into the central nucleus of the amygdala (CeA) inhibit food intake but this response is lost quickly on feeding a high fat diet. The purpose of the studies described in this manuscript was to identify the potential mechanism for the development of this insulin resistance. High fat diets (HFD) induced PKCθ activation and blocked the stimulation of Akt but not mTOR phosphorylation in the amygdala in response to CeA insulin injections. Infusions of palmitic acid onto the CeA had identical effects to HFD on PKCθ expression and insulin signaling in the amygdala. CeA insulin also induced an increase in Akt phosphorylation in the hypothalamus but had no effect on hypothalamic mTOR phosphorylation. Feeding HFD but not CeA palmitate infusions reversed the hypothalamic Akt signaling response to CeA insulin. These data, which show the independence of Akt and mTOR signaling responses to insulin in the amygdala and the effect of insulin signaling in the CeA on hypothalamic Akt signaling, suggest that the amygdala might also have a significant role in regulating hypothalamic responses to dietary fat.