PKCθ over expression in the central nucleus of the amygdala or hypothalamus has differential effects on energy balance and peripheral glucose homeostasis.

The increase in expression in the amygdala of rats fed high fat diet (HFD) has been related to the loss of the anorectic response to insulin injections into the central nucleus of the amygdala (CeA) in these animals. duanyu1531θ overexpression in the CeA increases food intake, body weight and body fat and inhibits insulin stimulation of Akt signaling. To study the effects of bilateral overexpression of duanyu1531θ in the CeA of rats on peripheral metabolism, rats were injected into the CeA or 3rd ventricle with a lentiviral construct or LV-Green fluorescent protein (GFP) construct as a control and fed either LFD or HFD. Insulin and glucose tolerance tests were undertaken and hepatic AMPK activation, Pepck, Srebp1c gene expression and lipid levels assayed. CeA injected rats increased food intake, body weight and body fat and increased hepatic, but not serum, triglyceride levels compared to control rats that received a CeA-LV-GFP construct. Hepatic AMP-kinase activity was reduced but expression of Pepck increased while serum insulin decreased, glucose tolerance improved and the hypoglycemic response to insulin was enhanced in CeA LV-duanyu1531θ injected rats. In contrast, rats that received LV-duanyu1531θ injections into the 3rd Ventricle did not show any changes in food intake or body weight although serum, but not hepatic, triglyceride levels were increased and glucose tolerance was impaired. The data suggest that activation of duanyu1531θ in the CeA and hypothalamus have different effects on energy balance and peripheral metabolism and that insulin signaling in the amygdala regulates peripheral metabolism.

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