Department of Endocrinology, Sawai Man Singh Medical College and Hospital, Jaipur 302004, India.
Department of Chemistry, School of Basic Sciences, Manipal University Jaipur, Jaipur 303007, India.
Biomolecules. 2020 Aug 24;10(9):1230. doi: 10.3390/biom10091230.
The roles of abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) in the molecular pathogenesis type-2 diabetics (T2D) among Asian Indians showing a "thin fat" phenotype largely remains obscure. In this study, we generated transcription profiles in biopsies of these adipose depots obtained during surgery in 19 diabetics (M: F ratio, 8:11) and 16 (M: F ratio 5:11) age- and BMI-matched non-diabetics. Gene set enrichment analysis (GSEA) was used for comparing transcription profile and showed that 19 gene sets, enriching inflammation and immune system-related pathways, were upregulated in diabetics with F.D.R. <25% and >25%, respectively, in VAT and SAT. Moreover, 13 out of the 19 significantly enriched pathways in VAT were among the top 20 pathways in SAT. On comparison of VAT vs. SAT among diabetics, none of the gene sets were found significant at F.D.R. <25%. The Weighted Gene Correlation Analysis (WGCNA) analysis of the correlation between measures of average gene expression and overall connectivity between VAT and SAT was significantly positive. Several modules of co-expressed genes in both the depots showed a bidirectional correlation with various diabetes-related intermediate phenotypic traits. They enriched several diabetes pathogenicity marker pathways, such as inflammation, adipogenesis, etc. It is concluded that, in Asian Indians, diabetes pathology inflicts similar molecular alternations in VAT and SAT, which are more intense in the former. Both adipose depots possibly play a role in the pathophysiology of T2D, and whether it is protective or pathogenic also depends on the nature of modules of co-expressed genes contained in them.
在表现出“瘦胖”表型的亚洲印第安人中，腹部内脏（VAT）和皮下脂肪组织（SAT）在 2 型糖尿病（T2D）的分子发病机制中的作用在很大程度上仍然不清楚。在这项研究中，我们在 19 名糖尿病患者（男女比例为 8:11）和 16 名（男女比例为 5:11）年龄和 BMI 匹配的非糖尿病患者手术时获得的这些脂肪组织活检中生成转录谱。基因集富集分析（GSEA）用于比较转录谱，结果显示，在 VAT 和 SAT 中，分别有 19 个基因集上调，这些基因集富集了炎症和免疫系统相关途径，其 FDR<25%和>F25%的糖尿病患者中上调。此外，在 VAT 中 19 个显著富集的通路中有 13 个也在 SAT 中位列前 20 个通路。在比较糖尿病患者的 VAT 与 SAT 时，在 FDR<25%时没有一个基因集是显著的。对 VAT 与 SAT 之间平均基因表达和整体连接之间的测量值进行加权基因相关性分析（WGCNA）分析，结果呈显著正相关。两个脂肪组织中表达相似的基因模块之间存在双向相关性，与各种与糖尿病相关的中间表型特征相关。它们富集了几个糖尿病发病机制标记途径，如炎症、脂肪生成等。结论是，在亚洲印第安人中，糖尿病病理在 VAT 和 SAT 中造成类似的分子改变，前者更为强烈。两个脂肪组织可能在 T2D 的病理生理学中发挥作用，其是否具有保护作用还是致病作用也取决于其中包含的共表达基因模块的性质。
