Papathomas Thomas G, Sun Na, Chortis Vasileios, Taylor Angela E, Arlt Wiebke, Richter Susan, Eisenhofer Graeme, Ruiz-Babot Gerard, Guasti Leonardo, Walch Axel Karl
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
Research Unit Analytical Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Histochem Cell Biol. 2019 Mar;151(3):201-216. doi: 10.1007/s00418-019-01772-w. Epub 2019 Feb 6.
Metabolic alterations have implications in a spectrum of tissue functions and disease. Aided by novel molecular biological and computational tools, our understanding of physiological and pathological processes underpinning endocrine and endocrine-related disease has significantly expanded over the last decade. Herein, we focus on novel metabolomics-related methodologies in adrenal research: in situ metabolomics by mass spectrometry imaging, steroid metabolomics by gas and liquid chromatography-mass spectrometry, energy pathway metabologenomics by liquid chromatography-mass spectrometry-based metabolomics of Krebs cycle intermediates, and cellular reprogramming to generate functional steroidogenic cells and hence to modulate the steroid metabolome. All four techniques to assess and/or modulate the metabolome in biological systems provide tremendous opportunities to manage neoplastic and non-neoplastic disease of the adrenal glands in the era of precision medicine. In this context, we discuss emerging clinical applications and/or promising metabolic-driven research towards diagnostic, prognostic, predictive and therapeutic biomarkers in tumours arising from the adrenal gland and extra-adrenal paraganglia as well as modern approaches to delineate and reprogram adrenal metabolism.
代谢改变对一系列组织功能和疾病都有影响。在新型分子生物学和计算工具的辅助下,在过去十年中,我们对内分泌及内分泌相关疾病所涉及的生理和病理过程的理解有了显著扩展。在此,我们聚焦于肾上腺研究中与代谢组学相关的新方法:基于质谱成像的原位代谢组学、气相和液相色谱 - 质谱联用的类固醇代谢组学、基于液相色谱 - 质谱联用对三羧酸循环中间体进行代谢物基因组学分析的能量途径代谢组学,以及通过细胞重编程生成功能性类固醇生成细胞从而调节类固醇代谢组。在精准医学时代,所有这四种评估和/或调节生物系统中代谢组的技术,都为管理肾上腺的肿瘤性和非肿瘤性疾病提供了巨大机遇。在此背景下,我们讨论新兴的临床应用和/或有前景的代谢驱动研究,以寻找肾上腺和肾上腺外副神经节肿瘤的诊断、预后、预测和治疗生物标志物,以及描绘和重编程肾上腺代谢的现代方法。