The role of macrophage metabolic reprogramming in regulating chronic inflammation and disease progression

Macrophages, as central components of the innate immune system, play a pivotal role in orchestrating inflammatory responses. Recent evidence highlights that macrophage function is closely governed by metabolic reprogramming, a process in which shifts in cellular metabolism modulate immune phenotypes and effector functions. During chronic inflammation, macrophages exhibit altered utilization of glycolysis, oxidative phosphorylation (OXPHOS), fatty acid oxidation, and glutamine metabolism. These metabolic shifts determine the polarization state of macrophages, driving pro-inflammatory (M۱-like) or anti-inflammatory (M۲-like) phenotypes. Persistent metabolic dysregulation contributes to uncontrolled inflammation and tissue damage in chronic diseases such as atherosclerosis, diabetes, rheumatoid arthritis, and cancer. In atherosclerosis, macrophages accumulate lipids and undergo metabolic stress that sustains inflammatory activation. In diabetes, hyperglycemia-induced metabolic reprogramming enhances macrophage glycolysis and inflammatory cytokine production. In tumors, the hypoxic microenvironment reshapes macrophage metabolism to support immunosuppressive and pro-tumorigenic activity. Understanding how metabolic pathways regulate macrophage function reveals therapeutic opportunities. Targeting key enzymes such as hexokinase ۲, isocitrate dehydrogenase, or AMP-activated protein kinase (AMPK) offers potential to reprogram macrophages toward inflammation resolution. This review integrates findings from immunometabolism and pathophysiology to demonstrate that macrophage metabolic reprogramming acts as a central mechanism linking cellular metabolism to chronic inflammation and disease progression. Therapeutic strategies that correct macrophage metabolic imbalance may provide novel approaches for managing chronic inflammatory disorders and improving patient outcomes.

کلیدواژه ها:

The role ، of macrophage metabolic ، reprogramming in regulating chronic ، inflammation and disease progression