The Transcriptomic Evidence on the Role of Abdominal Visceral vs. Subcutaneous Adipose Tissue in the Pathophysiology of Diabetes in Asian Indians Indicates the Involvement of Both

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.

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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

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2266 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Sandeep Kumar Mathur ◽

Anshul Kumar ◽

Pradeep tiwari ◽

aditya Saxena

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Asian Indians ◽

Gene Set Enrichment Analysis ◽

Phenotypic Traits ◽

Statistical Comparison ◽

Gene Sets ◽

Subcutaneous Adipose

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.

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Whole transcriptome RNA-seq reveals key regulatory factors involved in type 2 diabetes pathology in peripheral fat of Asian Indians

Scientific Reports ◽

10.1038/s41598-021-90148-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Aditya Saxena ◽

Nitish Mathur ◽

Pradeep Tiwari ◽

Sandeep Kumar Mathur

Keyword(s):

Type 2 Diabetes ◽

Adipose Tissue ◽

Transcription Factors ◽

Protein Kinases ◽

Subcutaneous Adipose Tissue ◽

Asian Indians ◽

Rna Seq ◽

Subcutaneous Adipose ◽

Upstream Regulators

AbstractThe prevalence of Type 2 Diabetes has reached an epidemic proportion particularly in south Asian countries. We have earlier shown that the anatomical fat distribution, termed ‘thin fat phenotype’ in this population indeed plays a major role for their T2D-predisposition it is indeed the sick fat or adiposopathy, which is the root cause of metabolic syndrome and diabetes and affects both—peripheral, as well as visceral adipose tissue compartments. In present study, we have attempted to unravel the altered regulatory mechanisms at the level of transcription factors, and miRNAs those may likely accounts to T2D pathophysiology in femoral subcutaneous adipose tissue. We prioritized transcription factors and protein kinases as likely upstream regulators of obtained differentially expressed genes in this RNA-seq study. An inferred network of these upstream regulators was then derived and the role of TFs and miRNAs in T2D pathophysiology was explored. In conclusions, this RNS-Seq study finds that peripheral subcutaneous adipose tissue among Asian Indians show pathology characterized by altered lipid, glucose and protein metabolism, adipogenesis defect and inflammation. A network of regulatory transcription factors, protein kinases and microRNAs have been imputed which converge on the process of adipogenesis. As the majority of these genes also showed altered expression in diabetics and some of them are also circulatory, therefore they deserve further investigation for potential clinical diagnostic and therapeutic applications.

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Inflammation and metabolism gene sets in subcutaneous abdominal adipose tissue are altered 1 hour after exercise in adults with obesity

Journal of Applied Physiology ◽

10.1152/japplphysiol.00943.2020 ◽

2021 ◽

Author(s):

Alison C. Ludzki ◽

Michael W. Schleh ◽

Emily M. Krueger ◽

Natalie M. Taylor ◽

Benjamin J. Ryan ◽

...

Keyword(s):

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Moderate Intensity ◽

Interval Exercise ◽

Continuous Exercise ◽

Gene Sets ◽

High Intensity Interval ◽

Subcutaneous Abdominal Adipose Tissue ◽

Subcutaneous Adipose ◽

Metabolism Gene

Although the health benefits of exercise in adults with obesity are well described, the direct effects of exercise on adipose tissue that may lead to improved metabolic health are poorly understood. The primary aims of this study were to perform an unbiased analysis of the subcutaneous abdominal adipose tissue transcriptomic response to acute exercise in adults with obesity, and to compare the effects of moderate-intensity continuous exercise vs. high-intensity interval exercise on this response. Twenty-nine adults with obesity performed a session of either high-intensity interval exercise (HI; 10x1 min at 90 %HRpeak, 1min recovery between intervals; n=14) or moderate-intensity continuous exercise (MI; 45 min at 70 %HRpeak; n=15). Groups were well-matched for BMI (HI 33±3 vs. MI 33±4 kg/m2), sex (HI: 9 women vs. MI: 10 women), and age (HI: 32±6 vs. MI: 29±5). Subcutaneous adipose tissue was collected before and 1 hour after the session of HI or MI, and samples were processed for RNA sequencing. Gene Set Enrichment Analysis revealed 7 of 21 gene sets enriched post-exercise overlapped between HI and MI. Interestingly, both HI and MI upregulated gene sets involved in inflammation (IL6-JAK-STAT3 signaling, allograft rejection, TNFA signaling via NFKB, and inflammatory response; FDR q-value<0.25). Exercise also downregulated adipogenic and oxidative metabolism gene sets in both groups. Overall, these data suggest genes involved in subcutaneous adipose tissue metabolism and inflammation may be an important part of the initial response after a session of exercise.

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Integrated Analysis of lncRNA and mRNA in Subcutaneous Adipose Tissue of Ningxiang Pig

Biology ◽

10.3390/biology10080726 ◽

2021 ◽

Vol 10 (8) ◽

pp. 726

Author(s):

Yan Gong ◽

Jun He ◽

Biao Li ◽

Yu Xiao ◽

Qinghua Zeng ◽

...

Keyword(s):

Fatty Acids ◽

Adipose Tissue ◽

Messenger Rna ◽

Subcutaneous Adipose Tissue ◽

Unsaturated Fatty Acids ◽

Integrated Analysis ◽

Transcription Profiles ◽

Non Coding Rna ◽

Similar Mode ◽

Subcutaneous Adipose

Ningxiang pigs, a Chinese bred pig known for its tender meat and high quality unsaturated fatty acids. This study discovers the transcription profiles and functional networks in long non-coding RNA (lncRNA) and messenger RNA (mRNA) in subcutaneous adipose tissue. Subcutaneous adipose tissue was collected from piglet, nursery pig, early fattening, and late fattening stage of Ningxiang piglets, and lncRNA and mRNA transcription of each stage was profiled. A total of 339,204,926 (piglet), 315,609,246 (nursery), 266,798,202 (early fattening), and 343,740,308 (late fattening) clean reads were generated, and 2872 novel lncRNAs were identified. Additionally, 10,084 differential mRNAs (DEmRNAs) and 931 differential lncRNAs were determined. Most DEmRNAs were up-regulated in the piglet stage, while they were down-regulated in late fattening stage. A complicated interaction between mRNAs and lncRNAs was identified via STEM and WGCNA, demonstrated that lncRNAs are a significant regulatory component in mRNAs. The findings showed that modules 2 and 5 have a similar mode of transcription for both mRNA and lncRNA, and were mainly participated in steroid biosynthesis, glycosphingolipid biosynthesis, metabolic pathways, and glycerolipid metabolism. The mRNAs and lncRNAs transcription levels of both modules was higher in the early and late fattening stage, which may be due to the active activity of the metabolism in relation to fatty acids, sterols, steroids, and lipids in the subcutaneous adipose tissue during the early and late fattening stage. These findings could be expected to result in further research of the functional properties of lncRNA from subcutaneous adipose tissue at different stages of development in Ningxiang pigs.

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