Maresin1 Alleviates Metabolic Dysfunction in Septic Mice: A ¹H NMR-Based Metabolomics Analysis

Area of Science:

• Biomedical Science
• Immunology
• Metabolomics

Background:

• Maresin1 (MaR1) is an anti-inflammatory lipid mediator with known organ-protective effects in sepsis.
• The precise mechanisms underlying MaR1's protective actions, particularly concerning metabolic alterations, remain incompletely understood.

Purpose of the Study:

• To investigate the impact of Maresin1 (MaR1) on metabolic dysfunction in mice subjected to cecal ligation and puncture (CLP)-induced sepsis.
• To elucidate the role of MaR1 in modulating inflammation and mitochondrial integrity during sepsis.

Main Methods:

• Utilized a cecal ligation and puncture (CLP) mouse model to induce sepsis.
• Administered Maresin1 (MaR1) to assess its therapeutic effects.
• Employed 1H NMR-based metabolomics to analyze serum and lung metabolic profiles.
• Measured levels of pro-inflammatory cytokines (TNF-α, IL-6) and assessed mitochondrial damage.

Main Results:

• Maresin1 (MaR1) significantly improved survival rates and attenuated lung and liver injuries in septic mice.
• MaR1 treatment reduced pro-inflammatory cytokine levels (TNF-α, IL-6) and alleviated mitochondrial damage.
• Metabolomic analysis revealed MaR1 reversed CLP-induced metabolic disturbances, including altered energy and amino acid metabolism, in serum and lungs.

Conclusions:

• Maresin1 (MaR1) demonstrates significant protective effects against sepsis-induced organ damage and mortality.
• The therapeutic benefits of MaR1 are associated with the restoration of metabolic homeostasis and the mitigation of inflammation and mitochondrial dysfunction.
• These findings highlight MaR1 as a potential therapeutic agent for sepsis, targeting key inflammatory and metabolic pathways.