Analysis of the Human Proteome in Subcutaneous and Visceral Fat Depots in Diabetic and Non-diabetic Patients with Morbid Obesity

Abstract

No longer regarded as simply a storage depot, fat is a dynamic organ acting locally and systemically to modulate energy homeostasis, glucose sensitivity, insulin resistance, and inflammatory pathways. Here, mass spectrometry was used to survey the proteome of patient matched subcutaneous fat and visceral fat in 20 diabetic vs 22 nondiabetic patients with morbid obesity. A similar number of proteins (~600) were identified in each tissue type. When stratified by diabetic status, 19 and 41 proteins were found to be differentially abundant in subcutaneous fat and omentum, respectively. These proteins represent pathways known to be involved in metabolism. Five of these proteins were differentially abundant in both fat depots: moesin, 78 kDa glucose-regulated protein, protein cordon-bleu, zinc finger protein 611, and cytochrome c oxidase subunit 6B1. Three proteins, decorin, cytochrome c oxidase subunit 6B1, and 78 kDa glucose-regulated protein, were further tested for validation by western blot analysis. Investigation of the proteins reported here is expected to expand on the current knowledge of adipose tissue driven biochemistry in diabetes and obesity, with the ultimate goal of identifying clinical targets for the development of novel therapeutic interventions in the treatment of type 2 diabetes mellitus. To our knowledge, this study is the first to survey the global proteome derived from each subcutaneous and visceral adipose tissue obtained from the same patient in the clinical setting of morbid obesity, with and without diabetes. It is also the largest study of diabetic vs nondiabetic patients with 42 patients surveyed.