The Proteomics-Based Stratification of Obese Subjects Allows for a Second Selective Level Beyond Gender...

Area of Science:

• Proteomics
• Metabolomics
• Biomarker Discovery

Background:

• Obesity is a global health issue linked to inflammation, oxidative stress, and cardiometabolic risks.
• Sex-based differences in obesity biomarkers exist, but underlying molecular mechanisms are unclear.

Purpose of the Study:

• To identify molecular signatures in urinary extracellular vesicles associated with metabolic dysregulation in obese individuals.
• To investigate sex-related molecular heterogeneity in obesity using proteomics.

Main Methods:

• Shotgun proteomics (nanoLC-MS/MS) on urinary extracellular vesicles from 45 obese individuals (BMI 30-40 kg/m², age 50-70).
• Hierarchical clustering to identify molecular groups, followed by label-free quantitative analysis.
• Functional enrichment analysis of differentially abundant proteins.

Main Results:

• Identified 3822 proteins; revealed two distinct clusters, predominantly male (Group I) and female (Group II).
• Found 466 differentially abundant proteins, enriched in pathways like immune response, metabolism, and redox homeostasis.
• Observed enrichment of ferroptosis-related proteins and higher non-enzymatic glycosylation in Group I, indicating increased advanced glycation products and oxidative stress.

Conclusions:

• Urinary proteomic profiling can distinguish molecular phenotypes in obesity.
• Oxidative stress, ferroptosis, and protein glycation are potential determinants of metabolic vulnerability.
• Non-invasive proteomics aids in improved risk stratification for obesity and related complications.