Department of Biology, Utah State University, Logan, Utah, USA.
Obesity (Silver Spring). 2013 Apr;21(4):755-64. doi: 10.1002/oby.20278.
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.
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.
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.
The data suggest that insulin may have a physiological role within the amygdala to regulate energy balance.
研究可能导致高脂肪饮食喂养 3 天后，胰岛素注射到杏仁中央核（CeA）引起厌食反应丧失的信号机制。
用高脂肪和低脂肪饮食喂养的大鼠的杏仁核和下丘脑的蛋白样本进行磷酸化筛选分析。研究膳食脂肪摄入对大脑区域蛋白激酶 Cθ（PKCθ）表达和激活的影响。最后，使用慢病毒载体将大鼠 PKCθ 单侧或双侧过表达到 CeA，研究其对食物摄入、体重和胰岛素刺激 Akt 磷酸化的影响。
高脂肪饮食喂养的大鼠杏仁核中 pMARCKS（蛋白激酶 Cθ的主要底物）的水平增加了 116%，而在下丘脑则降低。高脂肪饮食以特定于区域的方式增加了大脑中 PKCθ 的水平，并且这种 PKCθ 通过膜结合被激活。将大鼠 PKCθ 单侧或双侧过表达到 CeA 会抑制胰岛素刺激 Akt 信号，阻断胰岛素注射到杏仁核引起的厌食反应。与接受慢病毒-绿色荧光蛋白构建体的对照大鼠相比，双侧注射 PKCθ 的大鼠在高脂肪饮食喂养时体重和体脂增加更多，并且食物摄入增加。
数据表明，胰岛素可能在杏仁核中具有调节能量平衡的生理作用。
