A Proteomics Based Approach Reveals Differential Regulation of Visceral Adipose Tissue Proteins between Metabolically Healthy and Unhealthy Obese Patients

Abstract

Obesity and the metabolic disorders that constitute metabolic syndrome are a primary cause of morbidity and mortality in the world. Nonetheless, the changes in the proteins and the underlying molecular pathways involved in the relevant pathogenesis are poorly understood.In this study a proteomic analysis of the visceral adipose tissue isolated from metabolically healthy and unhealthy obese patients was used to identify presence of altered pathway(s) leading to metabolic dysfunction. Samples were obtained from 18 obese patients undergoing bariatric surgery and were subdivided into two groups based on the presence or absence of comorbidities as defined by the International Diabetes Federation. Two dimensional difference in-gel electrophoresis coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was carried out. A total of 28 proteins were identified with a statistically significant difference in abundance and a 1.5-fold change (ANOVA, p ≤ 0.05) between the groups. 11 proteins showed increased abundance while 17 proteins were decreased in the metabolically unhealthy obese compared to the healthy obese. The differentially expressed proteins belonged broadly to three functional categories: (i) protein and lipid metabolism (ii) cytoskeleton and (iii) regulation of other metabolic processes. Network analysis by Ingenuity pathway analysis identified the NFκB, IRK/MAPK and PKC as the nodes with the highest connections within the connectivity map. The top network pathway identified in our protein data set related to cellular movement, hematological system development and function, and immune cell trafficking. The VAT proteome between the two groups differed substantially between the groups which could potentially be the reason for metabolic dysfunction.

Differences in the Plasma Proteome of Patients with Hypothyroidism before and after Thyroid Hormone Replacement: A Proteomic Analysis

“…Engelmann et al experimentally induced thyrotoxicosis in healthy volunteers to explore the effects of l -thyroxine excess on the plasma proteome with a main focus on coagulation markers [ 11 ]. Therefore, the aim of our study was to evaluate changes in the plasma proteome in patients with hypothyroidism after replacement treatment with appropriate doses of l -thyroxine using the 2D-DIGE mass spectrometry approach [ 12 ]. Exploring the plasma proteome changes upon the transition from a hypothyroid to euthyroid state will help in understanding the thyroxine-mediated changes taking place in circulating proteins.…”

Differentially expressed serum proteins from obese Wistar rats as a risk factor for obesity-induced diseases

“…Several adipokines, cytokines, metabolites, and microRNAs are implicated in obesityinduced diseases, some are dysregulated in more than one disease while some show potential as disease-specific biomarkers. Their expression levels can identify individuals with or at risk of developing obesity-related diseases such as inflammatory diseases 8 , diabetes 9 , CVDs 10 and metabolically unhealthy obese people 11 .…”

“…Proteomics has been especially helpful in biomarker discovery for chronic diseases, not limited to cancer 12 , and obesity 11,13 . Proteomics provides a platform to study the entire proteome in a given sample, and allows for qualitative and quantitative protein profile that can discriminate between healthy and diseased samples 14 .…”

A Proteomics-Based Approach Reveals Differential Regulation of Urine Proteins between Metabolically Healthy and Unhealthy Obese Patients

“…Several reports on expression proteomics have shown that differential protein expression profiles exist in relation to different metabolic states [5,6,7]. In one study, a proteomic analysis of visceral fat tissue from obese people with and without metabolic syndrome (MetS) revealed that individuals characterized as MHO had an increased abundance of proteins related to adipose tissue expansion and antioxidant capacity.…”

“…In one study, a proteomic analysis of visceral fat tissue from obese people with and without metabolic syndrome (MetS) revealed that individuals characterized as MHO had an increased abundance of proteins related to adipose tissue expansion and antioxidant capacity. In comparison, the MUHO group showed increased abundance of proteins that related to mitochondrial and the lipid droplet metabolic activities [6]. In another study, 20 proteins were reported to be differentially expressed between MHO and MUHO individuals and most of these proteins were related to inflammatory and lipid processes [5].…”