State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Environ Pollut. 2023 Dec 1;338:122684. doi: 10.1016/j.envpol.2023.122684. Epub 2023 Oct 4.
Intestinal cell metabolism plays an important role in intestine health. Perfluorooctanoic acid (PFOA) exposure could disorder intestinal cell metabolism. However, the mechanisms regarding how the three carbon sources interact under PFOA stress remined to be understood. The present study aimed to dissect the interconnections of glucose, glutamine, and fatty acids in PFOA-treated human colorectal cancer (DLD-1) cells using C metabolic flux analysis. The abundance of glycolysis and tricarboxylic acid (TCA) cycle metabolites was decreased in PFOA-treated cells except for succinate, whereas most of amino acids were more abundant. Beside serine and glycine, the levels of metabolites derived from C glucose were reduced in PFOA-treated cells, and the pentose phosphate pathway flux was 1.4-fold higher in PFOA-treated cells than in the controls. In reductive glutamine pathway, higher labeled enrichment of citrate, malate, fumarate, and succinate was observed for PFOA-treated cells. The contribution of glucose to fatty acid synthesis in PFOA-treated cells decreased while the contribution of glutamine to fatty acid synthesis increased. Additionally, synthesis of TCA intermediates from fatty acid β-oxidation was promoted in PFOA-treated cells. All results suggested that metabolic remodeling could happen in intestinal cells exposed to PFOA, which was potentially related to PFOA toxicity relevant with the loss of glucose in biomass synthesis and energy metabolism.
肠道细胞代谢在肠道健康中发挥着重要作用。全氟辛酸（PFOA）暴露会扰乱肠道细胞代谢。然而，在 PFOA 应激下，三种碳源如何相互作用的机制仍有待阐明。本研究旨在使用 C 代谢通量分析来剖析 PFOA 处理的人结直肠癌细胞（DLD-1）中葡萄糖、谷氨酰胺和脂肪酸之间的相互联系。除琥珀酸外，PFOA 处理的细胞中糖酵解和三羧酸（TCA）循环代谢物的丰度降低，而大多数氨基酸更丰富。除丝氨酸和甘氨酸外，来源于 C 葡萄糖的代谢物水平在 PFOA 处理的细胞中降低，并且 PFOA 处理的细胞中戊糖磷酸途径通量比对照高 1.4 倍。在还原型谷氨酰胺途径中，PFOA 处理的细胞中观察到柠檬酸、苹果酸、富马酸和琥珀酸的标记丰度更高。在 PFOA 处理的细胞中，葡萄糖对脂肪酸合成的贡献减少，而谷氨酰胺对脂肪酸合成的贡献增加。此外，PFOA 处理的细胞中从脂肪酸β-氧化合成 TCA 中间产物的能力增强。所有结果表明，暴露于 PFOA 的肠道细胞可能会发生代谢重塑，这可能与 PFOA 毒性相关，即与生物量合成和能量代谢中葡萄糖的损失有关。
