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.

Transcriptomic analysis of visceral adipose from healthy and diabetic obese subjects.

Understanding the role of visceral fat accumulation in the occurrence and progression of metabolic syndrome is of considerable interest. In order to understand the difference between visceral tissue biology of healthy and unhealthy obese individuals, we have used microarray profiling to compare genome-wide expression differences between visceral adipose tissue biopsies obtained from obese diabetics, and those from age and body mass index (BMI) matched normal glucose tolerance subjects. Whereas genes upregulated in diabetics showed enrichment of natural killer cell mediated cytotoxicity, the downregulated genes showed enrichment of biosynthesis of unsaturated fatty acids. Given the known inhibitory effect of unsaturated fatty acids on inflammation and natural killer cell number or activity, our results suggest that visceral inflammation resulting from decreased levels of unsaturated fatty acids may underlie progression of diabetes in obese individuals.