Inverse Regulation of Inflammation and Mitochondrial Function in Adipose Tissue Defines Extreme Insulin Sensitivity in Morbidly Obese Patients

Qatanani, Mohammed
Tan, Yejun
Dobrin, Radu
Greenawalt, Danielle M.
Hu, Guanghui
Zhao, Wenqing
Olefsky, Jerrold M.
Sears, Dorothy D.
Kaplan, Lee M.
Kemp, Daniel M.

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Publication date

April 2014

DOI

10.2337/db12-0399.

Publisher

American Diabetes Association

Journal

Diabetes

Abstract

Obesity is associated with insulin resistance, a major risk factor for type 2 diabetes and cardiovascular disease. However, not all obese individuals are insulin resistant, which confounds our understanding of the mechanistic link between these conditions. We conducted transcriptome analyses on 835 obese subjects with mean BMI of 48.8, on which we have previously reported genetic associations of gene expression. Here, we selected ∼320 nondiabetic (HbA1c <7.0) subjects and further stratified the cohort into insulin-resistant versus insulin-sensitive subgroups based on homeostasis model assessment–insulin resistance. An unsupervised informatics analysis revealed that immune response and inflammation-related genes were significantly downregula...