Does exercise enhance maresin-1 production? A new direction in metabolic anti-inflammatory research

Abstract

Obesity is a major global health challenge characterized by chronic low-grade inflammation and metabolic dysfunction. Among lipid-derived mediators involved in inflammation resolution, maresin-1 (MaR1)—a specialized pro-resolving mediator derived from docosahexaenoic acid (DHA) and produced mainly by M2 macrophages—has attracted increasing attention due to its potent anti-inflammatory and metabolic regulatory properties. MaR1 promotes the resolution of inflammation by limiting neutrophil infiltration, enhancing macrophage efferocytosis, and shifting cytokine profiles toward an anti-inflammatory phenotype. In addition, it modulates metabolic pathways related to insulin sensitivity and skeletal muscle glucose uptake through signaling mechanisms involving Akt and AMP-activated protein kinase (AMPK). Reduced circulating levels of MaR1 have been consistently associated with metabolic disorders, including obesity, type 2 diabetes, and cardiovascular disease, highlighting its potential as a biomarker of metabolic health. Exercise is a cornerstone non-pharmacological strategy for obesity management and activates molecular pathways—such as AMPK and Sirtuin 1 (SIRT1)—that overlap with those regulated by MaR1. However, human studies examining how different exercise modalities influence MaR1 production remain scarce. This perspective highlights the mechanistic links between exercise and MaR1 biology and proposes a translational research agenda to investigate how aerobic, resistance, and high-intensity interval training modulate MaR1 levels. Understanding this exercise–MaR1 axis may help establish MaR1 as a biomarker of exercise responsiveness and support the development of targeted lifestyle interventions for metabolic disease management.