Division of Science, Pennsylvania State University, Berks Campus, Reading, PA 19610, USA.
Biomolecules. 2024 Aug 20;14(8):1037. doi: 10.3390/biom14081037.
Obesity remains one of the largest health problems in the world, arising from the excess storage of triglycerides (TAGs). However, the full complement of genes that are important for regulating TAG storage is not known. The gene encodes a glucose transporter that has been identified as a potential obesity gene through genetic screening. Yet, the tissue-specific metabolic functions of Glut1 are not fully understood. Here, we characterized the role of Glut1 in the fly brain by decreasing neuronal levels with RNAi and measuring glycogen and TAGs. flies had decreased TAG and glycogen levels, suggesting a nonautonomous role of Glut1 in the fly brain to regulate nutrient storage. A group of hormones that regulate metabolism and are expressed in the fly brain are insulin-like peptides (Ilps) 2, 3, and 5. Interestingly, we observed blunted and expression in neuronal flies, suggesting Glut1 functions in insulin-producing neurons (IPCs) to regulate whole-organism TAG and glycogen storage. Consistent with this hypothesis, we also saw fewer TAGs and glycogens and decreased expression of and in flies with IPC-specific . Together, these data suggest Glut1 functions as a nutrient sensor in IPCs, controlling TAG and glycogen storage and regulating systemic energy homeostasis.
肥胖仍然是世界上最大的健康问题之一，源于甘油三酯（TAG）的过度储存。然而，对于调节 TAG 储存至关重要的完整基因集合尚不清楚。该基因编码一种葡萄糖转运蛋白，通过遗传筛选被鉴定为潜在的肥胖基因。然而，Glut1 的组织特异性代谢功能尚未完全了解。在这里，我们通过 RNAi 降低神经元水平并测量糖原和 TAG 来表征 Glut1 在果蝇大脑中的作用。神经元 Glut1 敲低的果蝇的 TAG 和糖原水平降低，表明 Glut1 在果蝇大脑中具有非自主作用，以调节营养物质储存。一组调节代谢并在果蝇大脑中表达的激素是胰岛素样肽（Ilp）2、3 和 5。有趣的是，我们观察到神经元 Glut1 敲低的果蝇中 Ilp2 和 Ilp3 的表达减弱，表明 Glut1 在产生胰岛素的神经元（IPCs）中发挥作用，以调节整个机体的 TAG 和糖原储存。与这一假设一致，我们还在 IPC 特异性 Glut1 敲低的果蝇中看到更少的 TAG 和糖原，以及 Ilp2 和 Ilp3 的表达降低。这些数据表明，Glut1 作为 IPC 中的营养传感器发挥作用，控制 TAG 和糖原储存，并调节全身能量稳态。
