From Menopause to Molecular Dysregulation: Proteomic Insights into Obesity-Related Pathways—A Narrative Review

TL;DR

This review explores how proteomic changes during menopause may contribute to weight gain and obesity in women, highlighting potential targets for personalized interventions.

Contribution

The paper provides a synthesis of proteomic evidence linking inflammation and metabolic dysfunction to obesity in peri- and postmenopausal women.

Findings

Proteomic patterns associated with inflammation, metabolic dysfunction, and endothelial dysregulation were consistently observed in peri- and postmenopausal obesity.

Weight loss was linked to reduced levels of inflammatory markers like IL-6 and CRP, suggesting reversibility of some obesity-related inflammation.

Proteomic signatures highlight potential pathways for personalized interventions targeting menopausal weight gain.

Abstract

Peri- and postmenopausal women often experience unexplained weight gain despite maintaining consistent dietary and lifestyle habits. While the biological mechanisms underlying this phenomenon remain poorly understood, physiological and pathophysiological changes during the menopausal transition are likely contributors. Proteomic profiling holds potential for revealing key molecular pathways involved in the pathogenesis of obesity in this population. This review synthesizes current evidence on proteomic alterations linked to overweight and obesity in peri- and postmenopausal women. A structured literature search was performed across Ovid MEDLINE®, EMBASE, the Cochrane Library, and Scopus for studies published between October 2010 and March 2025. Eligible studies included original research involving overweight or obese peri- or postmenopausal women that reported proteomic data. Extracted information encompassed study design, participant characteristics, sample types, and proteomic findings. Identified proteins were cross-referenced with a prior review of consistently dysregulated proteins in obesity. Five studies met the inclusion criteria, collectively revealing consistent proteomic patterns associated with inflammation, metabolic dysfunction, and endothelial dysregulation. These included C-reactive protein, Tissue necrotic factor-alpha, interleukins, adiponectin, and endocan. Notably, one study demonstrated that weight loss led to reductions in IL-6, IL-1 receptor antagonist, and CRP, suggesting that obesity-related inflammation may be at least partially reversible. This review provides preliminary evidence linking chronic inflammation, metabolic dysregulation, and vascular stress to obesity in peri- and postmenopausal women. These proteomic signatures enhance understanding of menopausal weight gain and highlight the potential of proteomics to guide personalized interventions. However, larger, well-designed prospective studies are needed to confirm these associations and clarify causal pathways.