CONTEXT Patients with adult growth hormone deficiency (AGHD) are at increased risk of metabolic syndrome. Metabolic profiles in AGHD patients have been insufficiently evaluated. OBJECTIVE This work aims to explore serum metabolite profiles by metabolomics analysis and assess potential metabolites associated with recombinant human growth hormone (rhGH) treatment. METHODS Thirty-one AGHD patients and 31 healthy controls were enrolled. Untargeted ultra-performance liquid chromatography-coupled mass spectroscopy was conducted in all patients and controls at baseline and during 12 months of rhGH treatment in 11 AGHD patients. Data were processed by principal component analysis, variable importance in projection scoring, orthogonal partial least squares-discriminant analysis, and MetaboAnalyst 5.0. We further explored the associations between metabolites and clinical parameters. RESULTS Metabolomics indicated a distinct metabolic pattern between AGHD patients and healthy controls. The perturbed pathways mainly include the biosynthesis of unsaturated fatty acids, sphingolipid metabolism, glycerophospholipid metabolism, fatty acid elongation, degradation, and biosynthesis. rhGH treatment increased the levels of specific glycerophospholipids compounds and reduced fatty acid ester compounds. Significant correlations existed between the 40 identified metabolites and insulin-like growth factor-1 SD score (IGF-1 SDS), body composition, and glucose and lipid metabolism plasma markers. During rhGH treatment, there was a statistically significant negative correlation between deoxycholic acid glycine conjugate and waist-to-hip ratio, while a statistically significant positive correlation existed between decanoylcarnitine and serum low-density lipoprotein levels. CONCLUSION AGHD patients have unique metabolomic profiles. rhGH treatment alters the serum levels of several fatty acid compounds/amino acids, which may contribute to the improvement of metabolic status in AGHD patients.

中文翻译：

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基于高效液相色谱-质谱法的成人生长激素缺乏症代谢分析。

背景 成人生长激素缺乏症 (AGHD) 患者患代谢综合征的风险增加。AGHD 患者的代谢特征尚未得到充分评估。目的 这项工作旨在通过代谢组学分析探索血清代谢物谱，并评估与重组人生长激素（rhGH）治疗相关的潜在代谢物。方法 纳入 31 名 AGHD 患者和 31 名健康对照。在 11 名 AGHD 患者的基线和 12 个月的 rhGH 治疗期间，对所有患者和对照进行了非靶向超高效液相色谱-质谱分析。数据通过主成分分析、投影评分中的变量重要性、正交偏最小二乘判别分析和 MetaboAnalyst 5.0 进行处理。我们进一步探讨了代谢物与临床参数之间的关联。结果代谢组学表明 AGHD 患者和健康对照之间存在独特的代谢模式。扰动途径主要包括不饱和脂肪酸的生物合成、鞘脂代谢、甘油磷脂代谢、脂肪酸延伸、降解和生物合成。rhGH 治疗增加了特定甘油磷脂化合物的水平并减少了脂肪酸酯化合物的水平。40 种已鉴定的代谢物与胰岛素样生长因子-1 SD 评分 (IGF-1 SDS)、身体成分以及葡萄糖和脂质代谢血浆标志物之间存在显着相关性。rhGH治疗期间，脱氧胆酸甘氨酸结合物与腰臀比之间存在统计学上显着的负相关，而癸酰肉碱与血清低密度脂蛋白水平之间存在统计学上显着的正相关。结论 AGHD 患者具有独特的代谢组学特征。rhGH 治疗改变了几种脂肪酸化合物/氨基酸的血清水平，这可能有助于改善 AGHD 患者的代谢状态。