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.
BACKGROUND
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.


METHODS
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.


RESULTS
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 x 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 x 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.


CONCLUSIONS
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.
Wolfs
Marcel G M
MG
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.
Rensen
Sander S
SS
Bruin-Van Dijk
Elinda J
EJ
Verdam
Froukje J
FJ
Greve
Jan-Willem
JW
Sanjabi
Bahram
B
Bruinenberg
Marcel
M
Wijmenga
Cisca
C
van Haeften
Timon W
TW
Buurman
Wim A
WA
Franke
Lude
L
Hofker
Marten H
MH
D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis*; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D008076:Cholesterol, HDL; D007328:Insulin; D014280:Triglycerides