Body mass index-independent inflammation in omental adipose tissue associated with insulin resistance in morbid obesity.
BACKGROUND
Obesity is a strong risk factor for resistance to insulin-mediated glucose disposal, a precursor of type 2 diabetes and other disorders. However, not all obese individuals are insulin resistant. We sought to identify the molecular pathways that might cause obesity-associated insulin resistance in humans by studying the morbidly obese who were insulin sensitive versus insulin resistant, thereby eliminating obesity as a variable.


METHODS
Combining gene expression profiling with computational approaches, we determined the global gene expression signatures of omental and subcutaneous adipose tissue samples obtained from similarly obese patients undergoing gastric bypass surgery.


RESULTS
Gene sets related to chemokine activity and chemokine receptor binding were identified as most highly expressed in the omental tissue from insulin-resistant compared with insulin-sensitive subjects, independent of the body mass index. These upregulated genes included chemokines (C-C motif) ligand 2, 3, 4, and 18 and interleukin-8/(CC-X motif) ligand 8 and were not differentially expressed in the subcutaneous adipose tissues between the 2 groups of subjects. Insulin resistance, but not the body mass index, was associated with increased macrophage infiltration in the omental adipose tissue, as was adipocyte size, in these morbidly obese subjects.


CONCLUSIONS
Our findings have demonstrated that inflammation of the omental adipose tissue is strongly associated with insulin resistance in human obesity even in subjects with similar body mass index values.
Hardy
Olga T
OT
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Perugini
Richard A
RA
Nicoloro
Sarah M
SM
Gallagher-Dorval
Karen
K
Puri
Vishwajeet
V
Straubhaar
Juerg
J
Czech
Michael P
MP
D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D015992:Body Mass Index; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000378:metabolism* / Q000503:physiopathology; D009852:Omentum; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D012189:Retrospective Studies
D018925:Chemokines; D012313:RNA