School of Applied Sciences, State University of Campinas, UNICAMP, Brazil.
Department of Internal Medicine, State University of Campinas, UNICAMP, Brazil.
Metabolism. 2017 May;70:1-11. doi: 10.1016/j.metabol.2017.01.029. Epub 2017 Feb 3.
Protein tyrosine phosphatase 1B (PTP1B) has been extensively implicated in the regulation of body weight, food intake, and energy expenditure. The role of PTP1B appears to be cell and brain region dependent.
Herein, we demonstrated that chronic high-fat feeding enhanced PTP1B expression in the central nucleus of the amygdala (CeA) of rats compared to rats on chow. Knocking down PTP1B with oligonucleotide antisense (ASO) decreased its expression and was sufficient to improve the anorexigenic effect of insulin through IR/Akt signaling in the CeA. ASO treatment reduces body weight, fat mass, serum leptin levels, and food intake and also increases energy expenditure, without altering ambulatory activity. These changes were explained, at least in part, by the improvement of insulin sensitivity in the CeA, decreasing NPY and enhancing oxytocin expression. There was a slight decline in fasting blood glucose and serum insulin levels possibly due to leanness in rats treated with ASO. Surprisingly, the elevated plus maze test revealed an anxiolytic behavior after reduction of PTP1B in the CeA.
Thus, the present study highlights the deleterious role that the amygdalar PTP1B has on energy homeostasis in obesity states. The reduction of PTP1B in the CeA may be a strategy for the treatment of obesity, insulin resistance and anxiety disorders.
蛋白酪氨酸磷酸酶 1B（PTP1B）广泛参与体重、食物摄入和能量消耗的调节。PTP1B 的作用似乎依赖于细胞和脑区。
本文证明，与正常饮食喂养的大鼠相比，慢性高脂肪饮食喂养增强了大鼠杏仁中央核（CeA）中的 PTP1B 表达。用寡核苷酸反义（ASO）敲低 PTP1B 可降低其表达，并足以通过 CeA 中的 IR/Akt 信号改善胰岛素的厌食作用。ASO 治疗可降低体重、脂肪量、血清瘦素水平和食物摄入量，并增加能量消耗，而不改变运动活动。这些变化至少部分解释了 CeA 中胰岛素敏感性的改善，降低了 NPY 并增强了催产素的表达。由于 ASO 治疗的大鼠偏瘦，空腹血糖和血清胰岛素水平略有下降。令人惊讶的是，在 CeA 中降低 PTP1B 后，高架十字迷宫测试显示出一种抗焦虑行为。
因此，本研究强调了杏仁核 PTP1B 在肥胖状态下对能量平衡的有害作用。CeA 中 PTP1B 的减少可能是治疗肥胖症、胰岛素抵抗和焦虑症的一种策略。
