Omega-3 Lipid Mediators: Modulation of the M1/M2 Macrophage Phenotype and Its Protective Role in Chronic Liver Diseases

Abstract

The complex interplay between dietary factors, inflammation, and macrophage polarization is pivotal in the pathogenesis and progression of chronic liver diseases (CLDs). Omega-3 fatty acids (FAs) have brought in attention due to their potential to modulate inflammation and exert protective effects in various pathological conditions. Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown promise in mitigating inflammation and enhancing the resolution of inflammatory responses. They influence the M1/M2 macrophage phenotype balance, promoting a shift towards the M2 anti-inflammatory phenotype. Specialized pro-resolving mediators (SPMs), such as resolvins (Rvs), protectins (PDs), and maresins (MaRs), have emerged as potent regulators of inflammation and macrophage polarization. They show anti-inflammatory and pro-resolving properties, by modulating the expression of cytokines, facilitate the phagocytosis of apoptotic cells, and promote tissue repair. MaR1, in particular, has demonstrated significant hepatoprotective effects by promoting M2 macrophage polarization, reducing oxidative stress, and inhibiting key inflammatory pathways such as NF-κB. In the context of CLDs, such as nonalcoholic fatty liver disease (NAFLD) and cirrhosis, omega-3s and their SPMs have shown promise in attenuating liver injury, promoting tissue regeneration, and modulating macrophage phenotypes. The aim of this article was to analyze the emerging role of omega-3 FAs and their SPMs in the context of macrophage polarization, with special interest in the mechanisms underlying their effects and their interactions with other cell types within the liver microenvironment, focused on CLDs and the development of novel therapeutic strategies.