Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, Massachusetts, USA.
Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, Massachusetts, USA; Department of Chemistry, University of Alaska Anchorage, Anchorage, Alaska, USA.
J Biol Chem. 2022 Feb;298(2):101444. doi: 10.1016/j.jbc.2021.101444. Epub 2021 Nov 23.
The maintenance of optimal membrane composition under basal and stress conditions is critical for the survival of an organism. High-glucose stress has been shown to perturb membrane properties by decreasing membrane fluidity, and the membrane sensor PAQR-2 is required to restore membrane integrity. However, the mechanisms required to respond to elevated dietary glucose are not fully established. In this study, we used a C stable isotope-enriched diet and mass spectrometry to better understand the impact of glucose on fatty acid dynamics in the membrane of Caenorhabditis elegans. We found a novel role for monomethyl branched-chain fatty acids (mmBCFAs) in mediating the ability of the nematodes to survive conditions of elevated dietary glucose. This requirement of mmBCFAs is unique to glucose stress and was not observed when the nematode was fed elevated dietary saturated fatty acid. In addition, when worms deficient in elo-5, the major biosynthesis enzyme of mmBCFAs, were fed Bacillus subtilis (a bacteria strain rich in mmBCFAs) in combination with high glucose, their survival rates were rescued to wild-type levels. Finally, the results suggest that mmBCFAs are part of the PAQR-2 signaling response during glucose stress. Taken together, we have identified a novel role for mmBCFAs in stress response in nematodes and have established these fatty acids as critical for adapting to elevated glucose.
在基础和应激条件下维持最佳膜组成对于生物体的生存至关重要。高葡萄糖应激已被证明通过降低膜流动性来破坏膜性质，并且需要膜传感器 PAQR-2 来恢复膜完整性。然而，响应升高的膳食葡萄糖所需的机制尚未完全建立。在这项研究中，我们使用 C 稳定同位素富集饮食和质谱来更好地了解葡萄糖对秀丽隐杆线虫膜中脂肪酸动态的影响。我们发现单甲基支链脂肪酸 (mmBCFA) 在介导线虫在升高的膳食葡萄糖条件下生存能力方面具有新的作用。这种对 mmBCFA 的需求是葡萄糖应激所特有的，在喂食升高的膳食饱和脂肪酸时没有观察到这种需求。此外，当 elo-5 缺陷型线虫（mmBCFA 的主要生物合成酶）喂食富含 mmBCFA 的枯草芽孢杆菌（Bacillus subtilis）与高葡萄糖结合时，它们的存活率恢复到野生型水平。最后，结果表明 mmBCFAs 是葡萄糖应激期间 PAQR-2 信号响应的一部分。总之，我们已经确定了 mmBCFA 在线虫应激反应中的新作用，并将这些脂肪酸确定为适应升高的葡萄糖的关键。
