Dataset Information

SUN-LB106 The Transcriptomic Evidences on Role of Abdominal Visceral vs. Subcutaneous Adipose Tissue in the Pathophysiology of Diabetes in Asian Indian Indicates the Involvement of Both

ABSTRACT: Abstract Introduction: Asian Indians show “thin fat phenotype” characterized by higher visceral adipose tissue(VAT) and lower subcutaneous adipose tissue(SAT) mass and their higher cardio-metabolic risk has been attributed to this fat distribution. However, the underlying molecular pathology and role of these adipose depots in the pathogenesis of T2D in them remains unknown.Hypothesis: The comparison of transcription profiles of abdominal VAT and SAT and their correlation with diabetes related intermediate phenotypic traits could shed some light on their role in the pathophysiology of diabetes.MethodologySubjects: 19 diabetics (M: F ratio, 8:11) and 16 age and BMI matched controls (M: F ratio 5:11) undergoing abdominal surgery (non-malignant and non-infective conditions).Clinical Parameters: Anthropometry, Serum glucose, insulin, HOMA-R, HbA1c, lipid profile, FFA, adipocytokines. Abdominal VAT, SAT and liver fat were estimated by MRI.Adipose tissue biopsy: SAT and VAT samples were taken during surgery. Genome-wide gene expression profiling of these biopsies was performed using Affymetrix GeneChipPrimeView® arrays. The data was submitted to NCBI-GEO (Accession # GSE78721). Selected genes were validated by qPCR. Gene set enrichment analysis (GSEA) for functional and Weighted Gene Correlation Analysis (WGCNA) for statistical comparison was done.Results:Diabetics had higher waist circumference (p=0.05), HOMA-R (p=0.0002), Visceral fat content (p=0.02) and adipocyte size (p=0.02)GSEA: diabetics vs. controls: In VAT 16 gene sets were upregulated (FDR < 25%) enriching various immune system and inflammation-related pathways. In SAT too, various inflammatory genes were upregulated however they were statistically non-significant (FDR > 25%). Moreover, 12 out of 16 significantly enriched pathways in VAT were among the top 20 pathways in SAT. GSEA in diabetics: VAT vs SAT: None of the gene sets were found significant at FDR < 25% which substantiated our hypothesis that overall pathophysioloigcal alteration in both depots are similar. WGCNA for statistical comparison of VAT and SAT depots The correlation between measures of average gene expression and overall connectivity between both depots was significantly positive. Several modules of co-expressed genes in both VAT and SAT showed positive as well as negative correlation with various intermediate phenotypic traits of diabetes. In both depots they enriched several pathways otherwise known to be associated with pathological adipose tissue like inflammation, adipogenesis etc. Conclusions In Asian Indians, diabetes pathology inflicts similar molecular alternations in VAT and SAT, which are more intense in the former. The role of both adipose depots in the pathophysiology of diabetes is along similar lines and they enrich several molecular pathways which are otherwise known to be implicated in pathological adipose tissue.

SUBMITTER: Mathur S

PROVIDER: S-EPMC7209250 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio, our most significant p-value was rs11118316 at LYPLAL1 gene (p = 3.1 × 10E-09), previously identified in association with waist-hip ratio. For SAT, the most significant SNP was in the FTO gene (p = 5.9 × 10E-08). Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6 × 10-08), but not men (p = 0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006) but not men (p = 0.24) for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]). Finally, we interrogated our data for the 14 recently published loci for body fat distribution (measured by waist-hip ratio adjusted for BMI); associations were observed at 7 of these loci. In contrast, we observed associations at only 7/32 loci previously identified in association with BMI; the majority of overlap was observed with SAT. Genome-wide association for visceral and subcutaneous fat revealed a SNP for VAT in women. More refined phenotypes for body composition and fat distribution can detect new loci not previously uncovered in large-scale GWAS of anthropometric traits.

Dataset Information

SUN-LB106 The Transcriptomic Evidences on Role of Abdominal Visceral vs. Subcutaneous Adipose Tissue in the Pathophysiology of Diabetes in Asian Indian Indicates the Involvement of Both

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets