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

Hicham Benabdelkamel,Mohammed Y Al-Naami,Meshail Okla,Assim A Alfadda,Afshan Masood

doi:10.3390/ijms20194905

Hicham Benabdelkamel, Mohammed Y Al-Naami + Show 3 more

Open Access

https://doi.org/10.3390/ijms20194905

Copy DOI

Abstract

Metabolic dysfunction associated with obesity threatens to inundate health care resources by increasing the incidences of obesity-related diseases. The aim of the present study was to investigate the changes in the urinary proteome of 18 individuals classified into metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO) patients. Proteome analysis was performed using the two-dimensional difference in gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS). Upon analysis, a total of 54 proteins were found to be affected with ≥1.5-fold change (ANOVA, p ≤ 0.05), of which 44 proteins were upregulated and 10 proteins were downregulated. These differentially abundant proteins were related to nuclear factor κB (NF-κB) and p38 mitogen-activated protein (MAP) kinase pathways and were involved in cellular compromise, inflammatory response, and cancer. Proteins involved in inflammation (fibrinogen alpha (FIBA), serotransferrin (TRFE, and kininogen-1 (KNG1)) and insulin resistance (ADP-ribosylation factor (ARF)-like protein 15 (ARL15) and retinol-binding protein 4 (RET4)) were found to be significantly increased in the urine samples of MUHO compared to MHO patients. Investigating the effects of obesity on urinary proteins can help in developing efficient diagnostic procedures for early detection and prevention of obesity-related complications.

Highlights

Over the last 44 years, the worldwide prevalence of obesity has nearly tripled [1]
Our data showed that there was a significant increase in the levels of proteins involved in inflammation Fibrinogen Alpha Chain (FIBA), TRFE, and KNG1 and insulin resistance ARL15 and Retinol-Binding Protein 4 (RET4) in the urine samples of the metabolically unhealthy obese (MUHO) group compared to the metabolically healthy obese (MHO) group
We found that RET4 was affected by the metabolic state associated with obesity, as the MUHO group showed 1.5-fold higher levels of excreted RET4 in urine compared to the MHO group

Summary

Introduction

People who are obese, compared to those with a normal or healthy weight, are at increased risk of metabolic disorders such as insulin resistance, dyslipidemia, and hypertension. Obesity is associated with increased risk of developing comorbidities including diabetes and cardiovascular diseases. Accumulating evidence suggests that metabolically healthy obese (MHO) people were not at high risk of cardiovascular diseases as they displayed no metabolic abnormalities such as dyslipidemia, insulin resistance, hypertension, or a high degree of inflammation regardless of their high BMI [2,3]. MHO individuals demonstrated three clinical features—a reduced accumulation of visceral and ectopic fat for equal total adiposity, preserved insulin sensitivity, and a lower degree of systemic and adipose tissue inflammation compared to metabolically unhealthy obese (MUHO) people [2]. Metabolically healthy and unhealthy obese individuals displayed different phenotypes [2,3]

Objectives

Results

Discussion

Conclusion