Table 1.
Metabolic pathways of classically activated M1 macrophages and alternatively activated M2 macrophages.
| Immune cell | Metabolic pathway | Metabolic reprogramming | Relevance of metabolic pathway to cellular function | Model | References |
|---|---|---|---|---|---|
| M1 macrophages | Glycolysis | ⇑ | Inflammatory cytokines production | Myeloid-specific HIF-1α overexpressing mice | (139) |
| HFD-fed mice and myeloid-specific HIF-1α−/− mice | (140) | ||||
| Vascular remodeling | ATMs deletion in HFD-fed mice LPS and High Glucose stimulated macrophages |
(141) | |||
| Oxidative phosphorylation | ⇓ | (138) | |||
| Pentose phosphate pathway | ⇑ | Production of inflammatory cytokines, ROS and NO | Trypanosoma cruzi-infected macrophages | (142) | |
| Inflammatory cytokines production | Myeloid-specific HIF-1α overexpressing mice | (139) | |||
| TCA Cycle | Truncated | Production of prostaglandins, NO and ROS | (143) | ||
| Lipogenesis | ⇑ | Required for Inflammasome activation and production of inflammatory mediators | Cecal ligation puncture-induced endotoxic shock in SREBP-1a-deficient mice LPS stimulated macrophages from mutant mice |
(144) | |
| Required for Phagocytosis | SREBP-1a-deficient macrophages | (145) | |||
| Required for inflammasome activation | Polymicrobial sepsis UCP2−/− mouse model | (146) | |||
| Glutamine metabolism | ⇓ | Required for polarization and T cell recruitment | Glutamine synthase (GS)-inhibited macrophages and GS−/− macrophages | (147) | |
| Fatty acid oxidation | ⇑ | Inflammasome activation | NOX4-deficient mice | (148) | |
| M2 macrophages | Glycolysis | ⇑ | Not essential for polarization unless OXPHOS is affected | BMDMs and Raw264.7 cells | (149) |
| Oxidative phosphorylation | ⇑ | Required for polarization | BMDMs and Raw264.7 cells | (149) | |
| Glutamine metabolism | ⇑ | Required for polarization | (150) | ||
| Fatty acid oxidation | ⇑ | Required for polarization and activation of the anti-inflammatory program | STAT6–/– BMDMs, embryonic-derived myeloid progenitors and PGC-1β transgenic mice | (151) | |
| Essentiality for polarization ? |
(152–154) |
⇑, high metabolic rate; ⇓, low metabolic rate; ?, requires further investigation.