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甲状腺眼病患者眶内脂肪组织的代谢特征。

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

机构信息

Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Front Endocrinol (Lausanne). 2023 Aug 3;14:1151757. doi: 10.3389/fendo.2023.1151757. eCollection 2023.

Abstract

BACKGROUND

Thyroid 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.

METHOD

The 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.

RESULTS

In 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 -value < 0.05). The TED-related pathways identified included purine metabolism, beta-alanine metabolism, glutathione metabolism (-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.

CONCLUSION

The 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.

摘要

背景

甲状腺眼病(TED)是成人中最常见的眼眶疾病,其特征是眶内脂肪组织(OAT)的积累。它可导致眼睑退缩,甚至视力丧失。眼眶减压手术是治疗不活动期 TED 的主要方法,通过去除多余的 OAT。然而,由于对发病机制,特别是代谢特征的认识不清,缺乏手术以外的替代治疗方法。因此,我们进行了这项研究,以探讨 TED 患者 OAT 的代谢物含量和特征。

方法

本研究使用的 OAT 取自 7 名不活动期 TED 患者的眼眶减压手术。我们还从 5 名无自身免疫性甲状腺疾病、TED 或非炎症性疾病史的眼部手术样本中收集了对照 OAT。使用液相色谱-质谱联用仪测量靶向代谢物。随后,我们进行了差异代谢物检测分析和相关通路富集分析。

结果

在本研究中,共检测到所有参与者的 149 种代谢物图谱。TED 组和对照组之间有几个代谢物图谱存在显著差异,主要包括尿酸、氧化型谷胱甘肽、牛磺酸、二鸟苷酸、氧化型谷胱甘肽 2、尿嘧啶、己糖磷酸、1-甲基烟酰胺、D-景天庚酮糖 1,7-二磷酸、尿苷 5'-一磷酸(均 P 值<0.05)。鉴定出的与 TED 相关的途径包括嘌呤代谢、β-丙氨酸代谢、谷胱甘肽代谢(P 值均<0.05)。我们的研究发现了重叠和差异,包括尿酸和尿嘧啶,与以前研究中 TED 患者血液中的代谢物以及我们研究中发现的几种新的代谢物,如己糖磷酸、1-甲基烟酰胺、D-景天庚酮糖 1,7-二磷酸、尿苷 5'-一磷酸一致,与以前研究中从血液、OAT 或尿液样本中检测到的代谢物不同。

结论

本研究结果揭示了 TED 患者 OAT 的代谢特征。这些结果可能有助于确定 TED 的新治疗靶点,为超越眼科手术的替代治疗方法提供潜在途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c47/10435847/8687ad264348/fendo-14-1151757-g001.jpg

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