NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burn Institute, Harvard Medical School, Boston, MA 02114, USA.
Int J Mol Med. 2010 Aug;26(2):175-84. doi: 10.3892/ijmm_00000450.
In vivo magnetic resonance spectroscopy (MRS), a non-destructive biochemical tool for investigating live organisms, has yet to be used in the fruit fly Drosophila melanogaster, a useful model organism for investigating genetics and physiology. We developed and implemented a high-resolution magic-angle-spinning (HRMAS) MRS method to investigate live Drosophila at 14.1 T. We demonstrated, for the first time, the feasibility of using HRMAS MRS for molecular characterization of Drosophila with a conventional MR spectrometer equipped with an HRMAS probe. We showed that the metabolic HRMAS MRS profiles of injured, aged wild-type (wt) flies and of immune deficient (imd) flies were more similar to chico flies mutated at the chico gene in the insulin signaling pathway, which is analogous to insulin receptor substrate1-4 (IRS1-4) in mammals and less to those of adipokinetic hormone receptor (akhr) mutant flies, which have an obese phenotype. We thus provide evidence for the hypothesis that trauma in aging and in innate immune-deficiency is linked to insulin signaling. This link may explain the mitochondrial dysfunction that accompanies insulin resistance and muscle wasting that occurs in trauma, aging and immune system deficiencies, leading to higher susceptibility to infection. Our approach advances the development of novel in vivo non-destructive research approaches in Drosophila, suggests biomarkers for investigation of biomedical paradigms, and thus may contribute to novel therapeutic development.
体内磁共振波谱(MRS)是一种用于研究活体生物的非破坏性生化工具,但尚未在果蝇 Drosophila melanogaster 中使用,后者是研究遗传学和生理学的有用模式生物。我们开发并实施了一种高分辨率魔角旋转(HRMAS)MRS 方法,用于在 14.1 T 下研究活体果蝇。我们首次证明了使用配备 HRMAS 探头的常规磁共振谱仪对果蝇进行 HRMAS MRS 分子特征分析的可行性。我们表明,受伤、衰老的野生型(wt)果蝇和免疫缺陷(imd)果蝇的代谢 HRMAS MRS 图谱与胰岛素信号通路中 chico 基因发生突变的 chico 果蝇更为相似,这类似于哺乳动物中的胰岛素受体底物 1-4(IRS1-4),而与具有肥胖表型的肾上腺素能激素受体(akhr)突变果蝇的图谱不那么相似。因此,我们为以下假说提供了证据:衰老和先天免疫缺陷中的创伤与胰岛素信号有关。这种联系可能解释了与胰岛素抵抗相关的线粒体功能障碍以及创伤、衰老和免疫系统缺陷中发生的肌肉减少症,从而导致更高的感染易感性。我们的方法推进了在果蝇中开发新型非破坏性体内研究方法的发展,为研究生物医学范例提供了生物标志物,从而可能有助于新的治疗方法的开发。