Table_1_Metabolic features of orbital adipose tissue in patients with thyroid eye disease.docx

BackgroundThyroid eye disease (TED) is the most frequent orbital disease in adults and is characterized by the accumulation of orbital adipose tissue (OAT). It can lead to eyelid retraction or even vision loss. Orbital decompression surgery serves as the primary treatment for inactive TED by removing the excess OAT. However, there is a lack of alternative treatments to surgery due to the unclear understanding of the pathogenesis, particularly the metabolic features. Accordingly, our study was implemented to explore the content and features of metabolites of OATs from TED patients.MethodThe OATs used in the current study were obtained from the orbital decompression surgery of seven patients with inactive TED. We also collected control OATs from eye surgical samples of five individuals with no history of autoimmune thyroid diseases, TED, or under non-inflammatory conditions. The liquid chromatography mass spectrometer was used for the measurements of the targeted metabolites. Afterwards, we performed differential metabolite assay analysis and related pathway enrichment analysis.ResultsIn our study, a total of 149 metabolite profiles were detected in all participants. There were significant differences in several metabolite profiles between the TED group and the control group, mainly including uric acid, oxidized glutathione, taurine, dGMP, oxidized glutathione 2, uracil, hexose-phosphate, 1-methylnicotinamide, D-sedoheptulose 1,7-bisphosphate, and uridine 5′-monophosphate (all p-value < 0.05). The TED-related pathways identified included purine metabolism, beta-alanine metabolism, glutathione metabolism (p-values < 0.05). Our study found overlaps and differences including uric acid and uracil, which are in accordance with metabolites found in blood of patients with TED from previous study and several newly discovered metabolite by our study such as hexose-phosphate, 1-methylnicotinamide, D-sedoheptulose 1,7-bisphosphate, compared to those tested from blood, OAT, or urine samples reported in previous studies.ConclusionThe findings of our study shed light on the metabolic features of OAT in individuals with TED. These results may help identify new treatment targets for TED, providing potential avenues for developing alternative treatments beyond ophthalmic surgery.

背景甲状腺眼病（TED）是成人最常见的眼眶疾病，其特征为眼眶脂肪组织（OAT）的积累。TED可能导致眼睑退缩甚至视力丧失。眼眶减压术是治疗非活动性TED的主要手段，通过移除多余的OAT。然而，由于对发病机制，尤其是代谢特征的认知不清，缺乏手术之外的替代治疗方案。鉴于此，本研究旨在探讨TED患者OAT代谢物的内容和特征。方法在本研究中，使用的OAT来自七例非活动性TED患者的眼眶减压手术。我们还从无自身免疫性甲状腺疾病、TED病史或非炎症状态的眼部手术样本中收集了对照组的OAT。采用液相色谱质谱联用技术对靶向代谢物进行测量。随后，我们进行了差异代谢物分析及相关通路富集分析。结果在本研究中，共检测到149个代谢物谱。TED组和对照组在多个代谢物谱上存在显著差异，主要包括尿酸、氧化谷胱甘肽、牛磺酸、dGMP、氧化谷胱甘肽2、尿嘧啶、己糖磷酸、1-甲基烟酰胺、D-赤藓糖-1,7-二磷酸和尿苷5′-单磷酸（所有p值均小于0.05）。确定的TED相关通路包括嘌呤代谢、β-丙氨酸代谢、谷胱甘肽代谢（p值均小于0.05）。本研究发现尿酸和尿嘧啶等重叠与差异，这与先前研究中从TED患者的血液中发现的代谢物一致，并且与本研究中新发现的代谢物如己糖磷酸、1-甲基烟酰胺、D-赤藓糖-1,7-二磷酸相比，以及先前研究中报道的来自血液、OAT或尿液样本的测试结果。结论本研究揭示了TED患者OAT的代谢特征。这些结果有助于识别TED的新治疗靶点，为开发超出眼科手术的替代治疗方案提供了潜在途径。