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

Abstract

Background Obesity is a strong risk factor for resistance to insulin-mediated glucose disposal, a precursor of type 2 diabetes and other disorders. Objectives To identify molecular pathways that may cause such obesity-associated insulin resistance in human subjects, we exploited the fact that not all obese individuals are prone to insulin resistance. Thus the degree of obesity as a variable was removed by studying morbidly obese human subjects of similar BMI values who are insulin-sensitive versus insulin-resistant. Setting University Medical Center, United States 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 to insulin sensitive subjects, independent of BMI. These upregulated genes included chemokines CCL2, CCL3, CCL4, CCL18 and IL8/CXCL8, and were not differentially expressed in subcutaneous adipose tissues between the two groups of subjects. Strikingly, insulin resistance, but not BMI, was associated with increased macrophage infiltration in the omental adipose tissue, as was adipocyte size, in these morbidly obese subjects. Conclusions Our findings demonstrate that inflammation of omental adipose tissue is strongly associated with insulin resistance in human obesity even in subjects with similar BMI values. Increased omental fat mass may contribute to the amplified inflammatory response observed in this population.

Signature Genes in Macrodactyly through Transcriptome Network Analysis Reveal their Association of Lipid Metabolism

“…In macrodactyly expression data (GSE35820), total RNA of 4 pediatric patients, including a 15-month-old boy and an 8-year-old girl who underwent elective surgical debulking at Massachusetts General Hospital or at Children's Hospital Boston between June 2009 and April 2011, were extracted [10]. In the fat group (GSE15773 [17] and GSE13506 [18]), adipose tissue samples were taken from subcutaneous fat of lower abdominal wall. Whole adipose tissue was dissected to remove fibrotic tissue and obvious vasculature, and frozen in 0.5 cm 3 sections in liquid nitrogen.…”

“…Whole adipose tissue was dissected to remove fibrotic tissue and obvious vasculature, and frozen in 0.5 cm 3 sections in liquid nitrogen. The data of fat group 1 were mainly obtained from University of Massachusetts Memorial Medical Center, a tertiary care academic hospital in a metropolitan setting in central New England [17], while fat group 2 data were obtained from multiple hospitals including Helsinki and Turku University Hospitals and Utrecht Academic University Hospital [18]. In case of skin sample (GSE14905), full thickness skin tissues were obtained from ILSBio and Rockefeller University [19].…”

Influence of Vitamin D Deficiency on Cardiometabolic Risk in Obesity

“…Dysfunctional adipose tissue changes its standard endocrine pattern decreasing production of "defensive" adipokines such as adiponectin, and increasing secretion of "offensive" adipokines with pro-inflammatory, diabetogenic and proatherogenic properties [15][16][17][18][19][20][21]. The majority of pro-inflammatory adipokines is product of immune cells that populate adipose tissue [22].…”

Integration and Weighing of Omics Data for Obesity

“…Transcriptomic alterations were treated as separate data sets to account for possible differences in transcriptional alterations observed in these tissue samples [55][56][57][58][59][60][61][62].…”