Simard Chloé J, Touaibia Mohamed, Allain Eric Pierre, Hebert-Chatelain Etienne, Pichaud Nicolas
Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB E1A 3E9, Canada.
Atlantic Cancer Research Institute (ACRI), Moncton, NB E1C 8x3, Canada.
Metabolites. 2020 Oct 14;10(10):411. doi: 10.3390/metabo10100411.
Excess dietary carbohydrates are linked to dysregulation of metabolic pathways converging to mitochondria and metabolic inflexibility. Here, we determined the role of the mitochondrial pyruvate carrier (MPC) in the occurrence of this metabolic inflexibility in wild-type (WT) and MPC1-deficient (MPC1) flies that were exposed to diets with different sucrose concentrations for 15-25 days (Standard Diet: SD, Medium-Sucrose Diet: MSD, and High-Sucrose Diet: HSD). Our results showed that MPC1 flies had lower mitochondrial respiration rates than WT flies on the SD and MSD. However, when exposed to the HSD, WT flies displayed decreased mitochondrial respiration rates compared to MPC1 flies. WT flies exposed to the HSD also displayed increased proline contribution and slightly decreased expression. Surprisingly, when fed the MSD and the HSD, few metabolites were altered in WT flies whereas MPC1 flies display significant accumulation of glycogen, glucose, fructose, lactate, and glycerol. Overall, this suggests that metabolic inflexibility starts to occur in WT flies after 15-25 days of exposure to the HSD whereas the MPC1 flies display metabolic inflexibility independently of the diet provided. This study thus highlights the involvement of MPC as an essential protein in Drosophila to maintain proper metabolic homeostasis during changes in dietary resources.
过量的膳食碳水化合物与汇聚到线粒体的代谢途径失调和代谢灵活性受损有关。在此，我们确定了线粒体丙酮酸载体（MPC）在野生型（WT）和MPC1缺陷型（MPC1）果蝇发生这种代谢灵活性受损过程中的作用，这些果蝇被喂食不同蔗糖浓度的饲料15 - 25天（标准饲料：SD，中蔗糖饲料：MSD，高蔗糖饲料：HSD）。我们的结果表明，在SD和MSD上，MPC1果蝇的线粒体呼吸速率低于WT果蝇。然而……[原文此处表述不完整]，与MPC1果蝇相比，WT果蝇的线粒体呼吸速率降低。暴露于HSD的WT果蝇还表现出脯氨酸贡献增加和[原文此处表述不完整]表达略有降低。令人惊讶的是，当喂食MSD和HSD时，WT果蝇中几乎没有代谢物发生改变，而MPC1果蝇则表现出糖原、葡萄糖、果糖……[原文此处表述不完整]、乳酸和甘油的显著积累。总体而言，这表明WT果蝇在暴露于HSD 15 - 25天后开始出现代谢灵活性受损，而MPC1果蝇则独立于所提供的饮食表现出代谢灵活性受损。因此，这项研究突出了MPC作为果蝇中一种必需蛋白质在饮食资源变化期间维持适当代谢稳态中的作用。
