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转录组谱分析揭示了亚洲人体内周脂肪组织病变与 2 型糖尿病的关联。

Transcriptome profiling reveals association of peripheral adipose tissue pathology with type-2 diabetes in Asian Indians.

机构信息

a Department of Biotechnology , Institute of Applied Sciences and Humanities, GLA University , Mathura , India.

b Department of Endocrinology , Sawai Man Singh Medical College and Hospital , Jaipur , India.

出版信息

Adipocyte. 2019 Dec;8(1):125-136. doi: 10.1080/21623945.2019.1595269. Epub 2019 Mar 28.

Abstract

Type 2 diabetes (T2D) is a complex disease with an elusive link between its molecular aetiology and clinical presentation. Although, the role of visceral adipose tissue in insulin-resistance and T2D is known, limited information is available on the role of peripheral-subcutaneous adipose tissue especially in Asian Indians. In this microarray-based study of diabetic and normal glucose tolerant Asian Indians, we generated the transcriptome of their thigh adipose tissue and analyzed differentially expressed genes (DEGs) using weighted gene co-expression network analysis; further we identified perturbed pathways implicated by these DEGs in relevant co-expression modules. We also attempted to link these pathways with known aspects of T2D pathophysiology in terms of their association with some of their intermediate traits, namely; adipocyte size, HOMA-B, HOMA-R, Hb1Ac, insulin, glucose-level, TNF-α, IL-6, VLDLs, LDLs, HDLs, and NEFAs. It was observed that several modules of co-expressed genes show an association with diabetes and some of its intermediate phenotypic traits mentioned above. Therefore, these findings suggest a role of peripheral subcutaneous adipose tissue in the pathophsiology of T2D in Asian Indians. Additionally, our study indicated that the peripheral subcutaneous adipose tissue in diabetics shows pathologic changes characterized by adipocyte hypertrophy and up-regulation of inflammation-related pathways.

摘要

2 型糖尿病(T2D)是一种复杂的疾病,其分子病因学与临床表型之间存在难以捉摸的联系。虽然内脏脂肪组织在胰岛素抵抗和 T2D 中的作用是已知的,但关于外周皮下脂肪组织的作用,特别是在亚洲印第安人中的作用,信息有限。在这项基于微阵列的糖尿病和正常葡萄糖耐量亚洲印第安人的研究中,我们生成了他们大腿脂肪组织的转录组,并使用加权基因共表达网络分析对差异表达基因(DEG)进行了分析;进一步,我们确定了这些 DEG 在相关共表达模块中涉及的失调途径。我们还试图将这些途径与 T2D 病理生理学的已知方面联系起来,根据它们与一些中间特征的关联,即:脂肪细胞大小、HOMA-B、HOMA-R、Hb1Ac、胰岛素、血糖水平、TNF-α、IL-6、VLDLs、LDLs、HDLs 和 NEFAs。结果表明,几个共表达基因模块与糖尿病及其上述一些中间表型特征有关。因此,这些发现表明外周皮下脂肪组织在亚洲印第安人 T2D 的病理生理学中起作用。此外,我们的研究表明,糖尿病患者的外周皮下脂肪组织表现出病理变化,特征为脂肪细胞肥大和炎症相关途径的上调。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20a1/6768216/83a143765f78/kadi-08-01-1595269-g002.jpg

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