Body mass index-independent inflammation in omental adipose tissue associated with insulin resistance in morbid obesity - PubMed (original) (raw)

Comparative Study

Body mass index-independent inflammation in omental adipose tissue associated with insulin resistance in morbid obesity

Olga T Hardy et al. Surg Obes Relat Dis. 2011 Jan-Feb.

Abstract

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.

Copyright © 2011 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

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Figures

Figure 1

Figure 1

Expression of inflammation-related genes in omental adipose tissue from insulin resistant and insulin sensitive obese human subjects using microarray and RTqPCR. A. Heatmap representing normalized expression of genes identified by Microarray Computational Environment (MACE) as being significantly increased in omental adipose tissue from insulin resistant subjects and insulin sensitive human subjects. The genes are listed on the right. Expression levels above the mean for the gene are shown in red and expression levels below the mean for the gene are shown in green. B. Fold change in mRNA level of genes in omental adipose tissue of obese, insulin-resistant subjects (n=10) relative to obese, insulin-sensitive subjects (n=10) based on microarray data (white bars) and quantitative real-time analysis (black bars) performed by RTqPCR. ** P < 0.01; * P < 0.05.

Figure 2

Figure 2

Relationship between macrophage infiltration, adipocyte diameter and HOMA2-IR in omental adipose tissue. Immunohistochemical detection of CD68+ macrophages performed on omental adipose tissue samples obtained from obese human subjects undergoing gastric bypass surgery. A-B. CD68 staining of omental adipose tissue from a representative insulin sensitive (A) and insulin resistant (B) subject. Unlike in adipose tissue from insulin sensitive subject (A) macrophages are observed throughout the tissue (arrows) and arranged in crown-like structures (arrowhead) in the insulin resistant subject (B). Sections taken at 20x magnification. CF, Quantitative analysis of adipocyte diameter and macrophage infiltration in adipose tissue of insulin resistant and insulin sensitive obese human subjects. Adipocyte diameter was calculated from the perimeter measurement of 100 cells. Insulin sensitivity, as determined by HOMA2-IR, correlates with CD68+ macrophage infiltration (C) and adipocyte diameter (D). Body mass index (BMI) shows no correlation with macrophage infiltration (E) or adipocyte diameter (F). Data is an average of 10 histological fields using 10X objective (C or E).

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