Impact of Lipid Metabolism on Macrophage Polarization: Implications for Inflammation and Tumor Immunity

Abstract

Macrophage polarization is influenced by lipids, which also exert significant control over macrophage functions. Lipids and their metabolites are players in intricate signaling pathways that modulate macrophages’ responses to pathogens, phagocytosis, ferroptosis, and inflammation. This review focuses on lipid metabolism and macrophage functions and addresses potential molecular targets for the treatment of macrophage-related diseases. While lipogenesis is crucial for lipid accumulation and phagocytosis in M1 macrophages, M2 macrophages likely rely on fatty acid β-oxidation to utilize fatty acids as their primary energy source. Cholesterol metabolism, regulated by factors such as SREBPs, PPARs, and LXRs, is associated with the cholesterol efflux capacity and the formation of foam cells (M2-like macrophages). Foam cells, which are targets for atherosclerosis, are associated with an increase in inflammatory cytokines. Lipolysis and fatty acid uptake markers, such as CD36, also contribute to the production of cytokines. Enhancing the immune system through the inhibition of lipid-metabolism-related factors can potentially serve as a targeted approach against tumor cells. Cyclooxygenase inhibitors, which block the conversion of arachidonic acid into various inflammatory mediators, influence macrophage polarization and have generated attention in cancer research.

The arachidonic acid metabolome reveals elevation of prostaglandin E2 biosynthesis in colorectal cancer

“…20 In recent years, researchers have begun to focus on AA metabolism in tumor biological functions and immune regulation. 21,22 In this study, we established a targeted metabolomics method for detecting AA metabolites using LC-MS/MS. We investigated the AA metabolite profiles of serum and tissue samples from CRC patients and healthy individuals, finding that the PGE2 biosynthetic pathway was upregulated in CRC and was positively associated with macrophage infiltration.…”

Targeting Fatty Acid Synthase Reduces Aortic Atherosclerosis and Inflammation

“…The mechanistic process that facilitates cFAS impact on foam cell formation is currently unknown. However, prior work demonstrates that endogenous FAS in macrophages is essential for the retention of plasma membrane cholesterol, cellular adhesion, and migration, as well as recruitment into adipose tissue that facilitates chronic tissue in ammation induced by nutrient dense diets 50,[56][57][58][59][60] . In our study, we similarly observed that pharmacological inhibition of FAS with PTM in mice maintained on 42% high-fat diet dramatically reduced macrophage in ltration in both hepatic and white adipose tissue (Fig.…”

Novel immune cross-talk between inflammatory bowel disease and IgA nephropathy

“…The glycolytic metabolic pathway regulates the immune system [ 66 ]. Similar to lipid metabolism, glycolysis can adjust the macrophage activation state and cell function by regulating polarization [ 67 , 68 ]. However, the association between glycolysis and IgAN remains poorly understood.…”