The liver is critical in maintaining metabolic homeostasis, regulating both anabolic and catabolic processes of fats, proteins, and carbohydrates. The IQ motif containing GTPase activating protein 2 (IQGAP2) is a member of the IQGAP family. Of the three homologous isoforms, the IQGAP2 scaffolding protein is predominantly found in the liver. To characterize its role in regulating metabolism, Iqgap2-/-female and male mice, and their WT controls, were fed ad libitum or fasted for 24 hours. Hepatic gene expression, protein levels, and the metabolic response were compared between WT and Iqgap2-/-mice, using RT-qPCR, western blot analysis, and histological stains. We found that loss of IQGAP2 alters the phosphorylation of active glycogen synthase kinase 3 (GSK3) expression, a known regulator of glycogen synthesis and lipogenesis. Consistent with this result, Iqgap2-/-female mice displayed depletion of periportal glycogen even in the fed state. We also observed blunted expression of genes involved in glycogenesis and lipogenesis when IQGAP2 was deleted. Since GSK3 is known to regulate the activity of -catenin, we examined and found it to be reduced in Iqgap2-/-mice. Our findings demonstrate that IQGAP2 plays an important role in regulating glycogen synthesis.

中文翻译：

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包含GTPase活化蛋白2（IQGAP2）的脚手架蛋白IQ基序调节糖原代谢

肝脏对于维持代谢稳态，调节脂肪，蛋白质和碳水化合物的合成代谢和分解代谢过程至关重要。包含GTPase激活蛋白2（IQGAP2）的IQ模体是IQGAP家族的成员。在这三种同源亚型中，IQGAP2支架蛋白主要存在于肝脏中。为了表征其在调节代谢中的作用，对Iqgap2-/-雌性和雄性小鼠及其WT对照进行随意喂养或禁食24小时。使用RT-qPCR，Western印迹分析和组织学染色比较WT和Iqgap2-/-小鼠的肝基因表达，蛋白质水平和代谢反应。我们发现丢失IQGAP2会改变活性糖原合酶激酶3（GSK3）表达的磷酸化，这是糖原合成和脂肪形成的已知调节剂。与该结果一致，即使在进食状态下，Iqgap2-/-雌性小鼠也显示出门静脉糖原的消耗。当删除IQGAP2时，我们还观察到与糖原生成和脂肪生成有关的基因表达迟钝。由于已知GSK3可以调节-catenin的活性，因此我们检查发现Iqgap2-/-小鼠中GSK3的活性降低。我们的发现表明IQGAP2在调节糖原合成中起重要作用。