Co-expressed immune and metabolic genes in visceral and subcutaneous adipose tissue from severely obese individuals are associated with plasma HDL and glucose levels: a microarray study
- Equal contributors
1 Department of Pathology and Medical Biology, Medical Biology Section, Molecular Genetics, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands
2 NUTRIM School for Nutrition, Toxicology and Metabolism, Department of General Surgery, Maastricht University Medical Center, Maastricht, the Netherlands
3 Department of Genetics, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands
4 Department of Internal Medicine, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, the Netherlands
5 Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London E1 2AT, UK
BMC Medical Genomics 2010, 3:34 doi:10.1186/1755-8794-3-34Published: 5 August 2010
Excessive accumulation of body fat, in particular in the visceral fat depot, is a major risk factor to develop a variety of diseases such as type 2 diabetes. The mechanisms underlying the increased risk of obese individuals to develop co-morbid diseases are largely unclear.
We aimed to identify genes expressed in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) that are related to blood parameters involved in obesity co-morbidity, such as plasma lipid and glucose levels, and to compare gene expression between the fat depots.
Whole-transcriptome SAT and VAT gene expression levels were determined in 75 individuals with a BMI >35 kg/m2. Modules of co-expressed genes likely to be functionally related were identified and correlated with BMI, plasma levels of glucose, insulin, HbA1c, triglycerides, non-esterified fatty acids, ALAT, ASAT, C-reactive protein, and LDL- and HDL cholesterol.
Of the approximately 70 modules identified in SAT and VAT, three SAT modules were inversely associated with plasma HDL-cholesterol levels, and a fourth module was inversely associated with both plasma glucose and plasma triglyceride levels (p < 5.33 × 10-5). These modules were markedly enriched in immune and metabolic genes. In VAT, one module was associated with both BMI and insulin, and another with plasma glucose (p < 4.64 × 10-5). This module was also enriched in inflammatory genes and showed a marked overlap in gene content with the SAT modules related to HDL. Several genes differentially expressed in SAT and VAT were identified.
In obese subjects, groups of co-expressed genes were identified that correlated with lipid and glucose metabolism parameters; they were enriched with immune genes. A number of genes were identified of which the expression in SAT correlated with plasma HDL cholesterol, while their expression in VAT correlated with plasma glucose. This underlines both the singular importance of these genes for lipid and glucose metabolism and the specific roles of these two fat depots in this respect.