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^def) 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^def 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^def flies. WT flies exposed to the HSD also displayed increased proline contribution and slightly decreased MPC1 expression. Surprisingly, when fed the MSD and the HSD, few metabolites were altered in WT flies whereas MPC1^def 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^def 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.

中文翻译：

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线粒体丙酮酸载体在膳食蔗糖暴露的果蝇体内代谢僵硬的发生中的作用

饮食中过量的碳水化合物与收敛到线粒体的代谢途径失调和代谢僵硬有关。在这里，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 ^def）的果蝇中发生这种代谢僵化的作用，这些果蝇暴露于不同蔗糖浓度的日粮中15–25天（标准饮食：SD，中等蔗糖饮食：MSD和高蔗糖饮食：HSD）。我们的研究结果表明，MPC1^高清苍蝇有较低的线粒体呼吸速率比WT在SD和MSD苍蝇。但是，当暴露于HSD时，与MPC1 ^def相比，野生型果蝇的线粒体呼吸速率降低苍蝇。暴露于HSD的WT蝇也显示出脯氨酸的贡献增加，MPC1表达略有下降。令人惊讶地，供给的MSD和HSD时，很少代谢物改变了WT苍蝇而MPC1 ^DEF蝇显示糖原，葡萄糖，果糖，乳酸盐和甘油的显著积累。总体而言，这表明发生代谢僵化开始在WT后暴露于HSD的15-25天飞逝而MPC1^高清独立飞行提供的饮食显示代谢僵化。因此，本研究强调了MPC作为果蝇必需蛋白质的参与，以在饮食资源变化期间维持适当的代谢稳态。