Unit of Andrology and Reproductive Medicine, Department of Medicine, University of Padova, Padova, Italy.
Division of Endocrinology, Fondazione Policlinico Universitario "Agostino Gemelli" Scientific Hospitalization and Treatment Institute (IRCCS), Rome, Italy.
Front Endocrinol (Lausanne). 2023 May 26;14:1165741. doi: 10.3389/fendo.2023.1165741. eCollection 2023.
Metabolomics proposes to unveil the molecular machinery involved in each specific disease by the comprehensive analysis of low-molecular-weight metabolites in a biological sample. This narrative mini-review analyzes previous studies applying ultra-high-performance liquid chromatography-high-resolution mass spectrometry (HRMS)-based metabolomics to highlight different metabolic pathways involved in male hypogonadism and testosterone replacement therapy, both in the case of insulin-sensitive patients with primary hypogonadism and in the case of insulin-resistant patients with functional hypogonadism. In functional hypogonadism, metabolomics revealed that different biochemical pathways are affected. In detail, glycolysis is the most important biochemical process involved in these patients. Glucose metabolism is fueled by amino acid degradation, and gluconeogenesis is widely stimulated. Some important pathways, including glycerol, are compromised. Furthermore, mitochondrial electron transport is influenced, namely, by a decrease in ATP production. On the contrary, beta-oxidation of short- and medium-chain fatty acids does not represent an energy source in hypogonadal patients. Both lactate and acetyl-CoA are converted into ketone bodies, which increased immensely. However, carnosine and β-alanine are greatly reduced. These metabolic changes are associated with increased fatigue and mental confusion. After testosterone replacement therapy, a complete restoration is achieved for only a part of the metabolites. It is of note that only in patients with functional hypogonadism treated with testosterone are ketone bodies produced at high levels, so the symptoms sometimes reported by these patients after the beginning of the therapy (difficulty in concentrating, depressed mood, brain fog, and memory impairment) might represent a specific "keto flu-like" syndrome, related to the metabolic ketonic state.
代谢组学通过对生物样本中低分子量代谢物的综合分析，提出了揭示每种特定疾病相关分子机制的方法。本篇叙述性综述分析了之前应用超高效液相色谱-高分辨率质谱（HRMS）代谢组学的研究，以突出原发性性腺功能减退症胰岛素敏感患者和功能性性腺功能减退症胰岛素抵抗患者的不同代谢途径中涉及的不同代谢途径。在功能性性腺功能减退症中，代谢组学揭示了不同的生化途径受到影响。具体而言，糖酵解是这些患者中最重要的生化过程。葡萄糖代谢由氨基酸降解提供燃料，糖异生广泛受到刺激。一些重要的途径，包括甘油，受到影响。此外，线粒体电子传递受到影响，即 ATP 的产生减少。相反，短链和中链脂肪酸的β氧化在性腺功能减退患者中不是能量来源。乳酸和乙酰辅酶 A 都转化为酮体，酮体大量增加。然而，肉碱和 β-丙氨酸大大减少。这些代谢变化与疲劳和精神混乱增加有关。在接受睾丸激素替代治疗后，只有一部分代谢物得到完全恢复。值得注意的是，只有在接受睾丸激素治疗的功能性性腺功能减退症患者中才会产生高水平的酮体，因此这些患者在治疗开始后有时会报告的症状（注意力不集中、情绪低落、大脑雾和记忆力减退）可能代表一种特定的“酮流感样”综合征，与代谢酮症状态有关。
