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Differential gene expression between visceral and subcutaneous fat depots
G Atzmon1, X M Yang, R Muzumdar
1Institute for Aging Research & Diabetes Research and Training Center Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Abstract:
Abdominal obesity has been linked to the development of insulin resistance and Type 2 diabetes mellitus (DM2). By surgical removal of visceral fat (VF) in a variety of rodent models, we prevented insulin resistance and glucose intolerance, establishing a cause-effect relationship between VF and the metabolic syndrome. To characterize the biological differences between visceral and peripheral fat depots, we obtained perirenal visceral (VF) and subcutaneous (SC) fat from 5 young rats. We extracted mRNA from the fat tissue and performed gene array hybridization using Affymetrix technology with a platform containing 9 000 genes. Out of the 1 660 genes that were expressed in fat tissue, 297 (17.9 %) genes show a two-fold or higher difference in their expression between the two tissues. We present the 20 genes whose expression is higher in VF fat (by 3 - 7 fold) and the 20 genes whose expression is higher in SC fat (by 3 - 150 fold), many of which are predominantly involved in glucose homeostasis, insulin action, and lipid metabolism. We confirmed the findings of gene array expression and quantified the changes in expression in VF of genes involved in insulin resistance (PPARgamma leptin) and its syndrome (angiotensinogen and plasminogen activating inhibitor-1, PAI-1) by real-time PCR (qRT-PCR) technology. Finally, we demonstrated increased expression of resistin in VF by around 12-fold and adiponectin by around 4-fold, peptides that were not part of the gene expression platform. These results indicate that visceral fat and subcutaneous fat are biologically distinct.
Insights
Visceral fat (VF) and subcutaneous fat (SC) are biologically distinct. Gene expression differences in VF and SC fat highlight their unique roles in metabolic syndrome, insulin resistance, and Type 2 diabetes mellitus.
Area of Science:
- Metabolic Biology
- Molecular Endocrinology
Background:
- Abdominal obesity is associated with insulin resistance and Type 2 diabetes mellitus (DM2).
- Surgical removal of visceral fat (VF) in rodent models prevents insulin resistance and glucose intolerance, establishing a causal link between VF and metabolic syndrome.
Purpose of the Study:
- To characterize the biological differences between visceral fat (VF) and subcutaneous fat (SC) depots.
- To identify genes with differential expression between VF and SC tissues.
Main Methods:
- Gene expression profiling using Affymetrix arrays on mRNA from rat perirenal visceral (VF) and subcutaneous (SC) fat.
- Validation of key gene expression changes using quantitative real-time PCR (qRT-PCR).
Main Results:
- Out of 1,660 expressed genes, 297 (17.9%) showed at least a two-fold difference in expression between VF and SC fat.
- Identified 20 genes with higher expression in VF (3-7 fold) and 20 genes with higher expression in SC (3-150 fold), many involved in glucose homeostasis, insulin action, and lipid metabolism.
- Confirmed increased expression of insulin resistance-related genes (PPARgamma, leptin, angiotensinogen, PAI-1) in VF and demonstrated significantly higher resistin (12-fold) and adiponectin (4-fold) expression in VF.
Conclusions:
- Visceral fat and subcutaneous fat are biologically distinct tissue depots.
- Differential gene expression patterns underscore unique roles in metabolic regulation and disease pathogenesis.