Vieira Andre F C, Xatse Mark A, Murray Sofi Y, Olsen Carissa Perez
Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, MA 01609, USA.
Metabolites. 2023 Dec 6;13(12):1185. doi: 10.3390/metabo13121185.
A key response to glucose stress is an increased production of unsaturated fatty acids to balance the increase in saturated fatty acids in the membrane. The homolog of stearoyl-CoA desaturase, FAT-7, introduces the first double bond into saturated C18 fatty acids yielding oleic acid, and is a critical regulatory point for surviving cold and glucose stress. Here, we incorporated C stable isotopes into the diet of nematodes and quantified the C-labelled fatty acid using GC-MS and HPLC/MS-MS to track its metabolic response to various concentrations of glucose. Previous work has analyzed the membrane composition of when responding to mild glucose stress and showed few alterations in the overall fatty acid composition in the membrane. Here, in nematodes exposed to higher concentrations of glucose, a specific reduction in oleic acid and linoleic acid was observed. Using time courses and stable isotope tracing, the response of fatty acid metabolism to increasing levels of glucose stress is characterized, revealing the funneling of monounsaturated fatty acids to preserve the abundance of polyunsaturated fatty acids. Taken together, higher levels of glucose unveil a specific reduction in oleic and linolenic acid in the metabolic rewiring required to survive glucose stress.
对葡萄糖应激的一个关键反应是增加不饱和脂肪酸的产生，以平衡膜中饱和脂肪酸的增加。硬脂酰辅酶A去饱和酶的同源物FAT-7将第一个双键引入饱和C18脂肪酸中，生成油酸，是线虫在寒冷和葡萄糖应激下存活的关键调控点。在这里，我们将碳稳定同位素掺入线虫的饮食中，并使用气相色谱-质谱联用仪（GC-MS）和液相色谱-串联质谱联用仪（HPLC/MS-MS）对碳标记的脂肪酸进行定量，以追踪其对不同浓度葡萄糖的代谢反应。先前的研究分析了线虫在应对轻度葡萄糖应激时的膜组成，结果表明膜中总体脂肪酸组成几乎没有变化。而在此研究中，我们发现，在暴露于较高浓度葡萄糖的线虫中，油酸和亚油酸出现了特异性减少。通过时间进程和稳定同位素示踪，我们对脂肪酸代谢对葡萄糖应激水平升高的反应进行了表征，揭示了单不饱和脂肪酸的流向以维持多不饱和脂肪酸的丰度。综上所述，更高水平的葡萄糖揭示了在葡萄糖应激存活所需的代谢重编程中，油酸和亚麻酸会出现特异性减少。
