Modulating Matrix Metalloproteinase Activity in Obesity: Comparative Effects of Bariatric Surgery and GLP-1/GIP-Based Pharmacotherapy

TL;DR

This review compares how bariatric surgery and GLP-1/GIP drugs affect MMP activity and metabolic outcomes in obesity.

Contribution

The paper provides a comparative analysis of bariatric surgery and pharmacotherapy effects on MMPs in obesity.

Findings

Bariatric surgery reduces MMP-9 and normalizes MMP-2 activity, improving ECM and insulin sensitivity.

Pharmacological therapies achieve weight loss but have limited evidence on direct MMP modulation.

More research is needed on how modern drugs affect ECM remodeling in obesity.

Abstract

Obesity is a multifactorial metabolic disease characterized by chronic low-grade inflammation, extracellular matrix (ECM) dysfunction, and systemic metabolic dysregulation. Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, are key regulators of ECM remodeling and inflammation in obesity. This narrative review aimed to synthesize and critically discuss current evidence on the effects of bariatric surgery and pharmacological therapies, including GLP-1 and dual GLP-1/GIP receptor agonists, on MMP activity and metabolic outcomes. Literature from PubMed and Scopus and Web of Science (2015–2024) was analyzed, focusing on studies evaluating MMPs, inflammation, and metabolic parameters. Bariatric surgery consistently reduces MMP-9 levels and normalizes MMP-2 activity, contributing to improved ECM integrity, reduced inflammation, and enhanced insulin sensitivity. Pharmacological therapies achieve substantial weight loss and glycemic control, but evidence regarding their direct effects on MMP activity remains limited. This review highlights bariatric surgery as the most effective strategy for modulating obesity-related MMP dysregulation and emphasizes the need for further research into the mechanistic effects of modern pharmacotherapy on ECM remodeling.