TY - JOUR
T1 - Body mass index-independent inflammation in omental adipose tissue associated with insulin resistance in morbid obesity
AU - Hardy, Olga T.
AU - Perugini, Richard A.
AU - Nicoloro, Sarah M.
AU - Gallagher-Dorval, Karen
AU - Puri, Vishwajeet
AU - Straubhaar, Juerg
AU - Czech, Michael P.
N1 - Funding Information:
Supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases (grant DK30898 to M. P. Czech), Worcester Foundation for Biomedical Research Grant Award (to R. A. Perugini), and the UMass Center for Clinical and Translational Science (to R. A. Perugini and O. T. Hardy). Core resources (Bioinformatics, Genomics, and Morphology) and a pilot grant (grant DK32520 ) supported by the Diabetes Endocrinology Research Center were also used.
PY - 2011/1
Y1 - 2011/1
N2 - 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. Conclusion: 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.
AB - 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. Conclusion: 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.
KW - Abdominal adipose tissue
KW - Chemokines
KW - Inflammation
KW - Insulin resistance
KW - Macrophages
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U2 - 10.1016/j.soard.2010.05.013
DO - 10.1016/j.soard.2010.05.013
M3 - Article
C2 - 20678967
AN - SCOPUS:78751649211
SN - 1550-7289
VL - 7
SP - 60
EP - 67
JO - Surgery for Obesity and Related Diseases
JF - Surgery for Obesity and Related Diseases
IS - 1
ER -