PKCθ expression in the amygdala regulates insulin signaling, food intake and body weight.

OBJECTIVE

To investigate the signaling mechanisms that might underlie the loss of anorectic response to insulin injections into the central nucleus of the amygdala (CeA) within 3 days of feeding a high fat diet.

DESIGN AND METHODS

Protein samples from amygdala and hypothalamus of rats fed high or low fat diets were subjected to a phosphorylation screening assay. The effects of dietary fat intake on the expression and activation of protein kinase C theta (PKCθ) in brain regions was studied. Finally, lentiviral vectors were used to overexpress rat PKCθ unilaterally or bilaterally into the CeA of rats and the effects on food intake, body weight and insulin stimulation of Akt phosphorylation were studied.

RESULTS

The level of pMARCKS (Myristoylated alanine-rich C-kinase substrate), a major substrate of PKCθ, was increased 116% in amygdala of high fat diet fed rats but reduced in the hypothalamus. High fat diets increased the level of PKCθ in a region specific manner in the brain and this PKCθ was activated by membrane association. Overexpressing rat PKCθ either unilaterally or bilaterally into the CeA inhibited insulin stimulation of Akt signaling and blocked the anorectic response to insulin injected into the amygdala. Bilaterally injected PKCθ rats gained more weight and body fat and had increased food intake when fed a high fat diet compared to the control rats that received a lentiviral-Green Fluorescent Protein construct.

CONCLUSION

The data suggest that insulin may have a physiological role within the amygdala to regulate energy balance.