Laboratory of Molecular Biology of Exercise (LaBMEx), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.
Laboratory of Nutritional Genomics (LabGeN), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.
Cytokine. 2018 Oct;110:87-93. doi: 10.1016/j.cyto.2018.04.013. Epub 2018 Apr 26.
Adiponectin is considered an adipokine that has essential anti-inflammatory and insulin-sensitivity actions. The adaptor protein containing the pleckstrin homology domain, the phosphotyrosine-binding domain, and leucine zipper motif 1 (APPL1) is a protein involved in adiponectin signaling that plays a role in many physiological and pathophysiological processes. In the central nervous system, adiponectin can potentiate the effects of leptin in the arcuate proopiomelanocortin (POMC) neurons. However, the role of APPL1 in the hypothalamus is not well understood. Therefore, in this study, we explored the effects of acute physical exercise on APPL1 protein content in the hypothalamus and food intake control in leptin stimulated-obese mice. Here we show that acute exercise increased serum adiponectin levels and APPL1 content in the hypothalamus, which were followed by reduced food intake in obese mice. Further, at the molecular level, the exercised obese mice increased the protein kinase B (Akt) signaling in the hypothalamus and attenuated the mammalian homolog of Drosophila tribbles protein 3 (TRB3) levels. In conclusion, the results indicate physical exercise is capable of increasing APPL1 protein content in the hypothalamus of leptin stimulated-obese mice and modulating food intake.
脂联素被认为是一种脂肪因子，具有重要的抗炎和胰岛素敏感性作用。含有pleckstrin 同源结构域、磷酸酪氨酸结合结构域和亮氨酸拉链基序 1（APPL1）的衔接蛋白是一种参与脂联素信号转导的蛋白质，在许多生理和病理生理过程中发挥作用。在中枢神经系统中，脂联素可以增强弓状核 proopiomelanocortin（POMC）神经元中瘦素的作用。然而，APPL1 在下丘脑中的作用尚不清楚。因此，在这项研究中，我们探讨了急性运动对下丘脑 APPL1 蛋白含量和瘦素刺激肥胖小鼠摄食控制的影响。结果显示，急性运动增加了肥胖小鼠血清脂联素水平和下丘脑 APPL1 含量，继而减少了肥胖小鼠的摄食量。此外，在分子水平上，运动肥胖小鼠增加了下丘脑蛋白激酶 B（Akt）信号通路，并降低了哺乳动物果蝇 tribbles 蛋白 3（TRB3）的水平。总之，这些结果表明，运动能够增加瘦素刺激肥胖小鼠下丘脑 APPL1 蛋白含量，并调节摄食。
