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

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.

2型糖尿病(Type 2 diabetes, T2D)是一类复杂疾病，其分子病因与临床表现之间的关联尚不明晰。尽管内脏脂肪组织(visceral adipose tissue)在胰岛素抵抗与2型糖尿病发病中的作用已被阐明，但目前针对外周皮下脂肪组织的相关研究仍较为有限，针对印度裔亚洲人群的相关数据尤为匮乏。本研究针对印度裔亚洲糖尿病患者与糖耐量正常人群开展基于微阵列的转录组学研究，采集其大腿脂肪组织进行转录组分析，并通过加权基因共表达网络分析筛选差异表达基因(differentially expressed genes, DEGs)，进而鉴定出这些差异基因在相关共表达模块中参与的失调通路。此外，本研究还尝试将这些通路与2型糖尿病病理生理学的已知特征进行关联，探讨其与多项中间表型的相关性，具体包括：脂肪细胞大小、HOMA-B、HOMA-R、糖化血红蛋白(Hb1Ac)、胰岛素、血糖水平、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、极低密度脂蛋白(VLDLs)、低密度脂蛋白(LDLs)、高密度脂蛋白(HDLs)以及游离脂肪酸(NEFAs)。研究结果显示，多个共表达基因模块与糖尿病及其上述部分中间表型存在显著关联。因此，本研究结果提示，外周皮下脂肪组织在印度裔亚洲人群的2型糖尿病病理生理过程中发挥着重要作用。此外，本研究还发现，糖尿病患者的外周皮下脂肪组织呈现以脂肪细胞肥大及炎症相关通路上调为特征的病理性改变。