Carrasco-García Álvaro, Herrera Guadalupe, de Graaff Laura C G, Visser Jenny A, Dasí Francisco, Codoñer-Franch Pilar
Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Valencia, Spain.
Flow Cytometry Unit, Fundación Investigación Hospital Clínico Valencia, Instituto de Investigación Sanitaria INCLIVA-UCIM, University of Valencia, Spain.
Free Radic Biol Med. 2025 Sep;237:397-402. doi: 10.1016/j.freeradbiomed.2025.06.014. Epub 2025 Jun 11.
Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by severe obesity and associated with increased oxidative stress. This phenomenon is partly attributed to elevated levels of reactive oxygen species (ROS), which promote inflammation and metabolic dysfunction, contributing to significant metabolic complications. Growth hormone (GH) treatment is widely used in children with PWS due to its well-documented benefits, including improvements in body composition, motor development, and cognitive function. In this study, we assessed the oxidative stress profile in children with PWS treated with GH. Since obesity and inflammation are well-established contributors to oxidative stress, values obtained from non-syndromic obese patients were included as a reference, allowing the findings to be contextualized within the framework of oxidative stress. The study included 12 GH-treated PWS children with a mean age of 15 years and 11 non-syndromic obese patients with a mean age of 14 years. Flow cytometry was employed as the primary method to analyse markers of oxidative stress, inflammation, and mitochondrial function in both groups. Additionally, this technique enabled the identification of immune cell populations associated with chronic inflammation, acute inflammation, and immune response, providing a comprehensive understanding of the underlying mechanisms. Despite PWS children having 4- to 6-fold lower glutathione (GSH) levels, PWS children demonstrated 2- to 3.5-fold higher mitochondrial activity, increasing their antioxidant capacity and reducing lipid peroxidation and protein carbonylation by up to 2-fold compared to non-syndromic obese children. GH-treated PWS children also showed lower mitochondrial dysfunction under oxidative conditions, higher cell viability, and elevated inflammatory biomarkers, suggesting a link to senescence and premature ageing. GH-treated PWS children, despite being non-obese, exhibited higher systemic inflammation compared to the non-syndromic obese group, alongside significant differences in oxidative stress and inflammatory markers. These findings suggest that mitochondrial pathways may play a role in antioxidant responses in PWS, highlighting the complexity of oxidative stress and its potential contribution to premature ageing in this condition. Understanding these mechanisms and the role of GH treatment could inform the development of targeted therapies to better manage oxidative stress and inflammation, ultimately improving the quality of life for PWS children.
普拉德-威利综合征（PWS）是一种罕见的遗传性疾病，其特征为严重肥胖，并伴有氧化应激增加。这种现象部分归因于活性氧（ROS）水平升高，ROS会促进炎症和代谢功能障碍，进而导致严重的代谢并发症。生长激素（GH）治疗因其已被充分证明的益处，包括改善身体成分、运动发育和认知功能，而被广泛应用于患有PWS的儿童。在本研究中，我们评估了接受GH治疗的PWS儿童的氧化应激状况。由于肥胖和炎症是氧化应激的既定促成因素，因此将非综合征性肥胖患者的数据作为参考纳入，以便在氧化应激框架内对研究结果进行背景化分析。该研究纳入了12名接受GH治疗的PWS儿童，平均年龄为15岁，以及11名非综合征性肥胖患者，平均年龄为14岁。流式细胞术被用作分析两组氧化应激、炎症和线粒体功能标志物的主要方法。此外，该技术能够识别与慢性炎症、急性炎症和免疫反应相关的免疫细胞群体，从而全面了解潜在机制。尽管PWS儿童的谷胱甘肽（GSH）水平比非综合征性肥胖儿童低4至6倍，但PWS儿童的线粒体活性却高2至3.5倍，这提高了他们的抗氧化能力，并使脂质过氧化和蛋白质羰基化降低了多达2倍。接受GH治疗的PWS儿童在氧化条件下还表现出较低的线粒体功能障碍、较高的细胞活力和升高的炎症生物标志物，这表明与衰老和早衰存在关联。接受GH治疗的PWS儿童尽管并不肥胖，但与非综合征性肥胖组相比，表现出更高的全身炎症，同时在氧化应激和炎症标志物方面存在显著差异。这些发现表明，线粒体途径可能在PWS的抗氧化反应中发挥作用，凸显了氧化应激的复杂性及其在这种情况下对早衰的潜在影响。了解这些机制以及GH治疗的作用，可为开发针对性疗法提供参考，以更好地管理氧化应激和炎症，最终改善PWS儿童的生活质量。
