Table 2 Roles of different metabolic profiles in macrophage phenotype and function. BMDMs, bone marrow-derived macrophages; MoDMs, human monocyte-derived macrophages; PMs, peritoneal macrophages
Experimental model(s) | Stimulation(s) | Regulator(s) | Effect(s) | Inhibitor(s) |
|---|---|---|---|---|
Arginine metabolism | ||||
 BMDMs/MoDMs | LPS/IFNγ | iNOS | NO blunts mitochondrial respiration and prevent M1 repolarization to the M2 phenotype (11) |  |
 BMDMs | LPS/IFNγ | iNOS | NO contributes to ETC impairment and promote protective processes to mitigate NO-induced damage (12) |  |
Glycolysis | ||||
 RAW264.7 | GLUT1 overexpression | GLUT1 | GLUT1-OE macrophages enhance inflammatory cytokine release (22) | 2DG(Glycolysis inhibitor) |
 PMs | Elicited by Brewer thioglycollate broth injection | glycolysis | Elicited macrophages have higher levels of glycolysis, which may be related to their increased phagocytic capacity (23) | 2DG(Glycolysis inhibitor) |
 PMs /mouse  J774A.1 macrophages  /BMDMs/THP1 | LPS and ATP | HK1 | HK1-dependent glycolysis is critical for NLRP3 inflammasome activation (27) | 2DG(Glycolysis inhibitor) |
 BMDMs | LPS and ATP | HK | HK dissociation is sufficient to induce NLRP3 inflammasome activation (28) |  |
 PMs /  BMDMs | IFN or VSV | PFKFB3 | PFKFB3-driven glycolysis selectively promotes the extrinsic antiviral capacity of macrophages (29) | PFK15(PFKFB3 inhibitor) |
 BMDMs/RAW264.7 | tuberculosis (TB) infection | PFK-M | PFK-M dependent glycolysis drives host defense (30) |  |
 BMDMs | LPS | GAPDH | GAPDH regulates TNFα production (31) |  |
 BMDMs | LPS | PKM2 | Activation of PKM2 promotes M1 polarization to the M2 macrophage and inhibites LPS-induced IL-1β (32) | DASA-58 and TEPP-46(PKM2 activators) |
 BMDMs/THP1/PMs | LPS+ATP or dA:dT | PKM2 | PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation (33) | Shikonin (PKM2 inhibitor) |
TCA cycle | ||||
 BMDMs/PMs/RAW264.7 | LPS/IL-4 | PDK1 | Knockdown of PDK1 diminishes M1, whereas it enhances M2 activation (34) | 2DG(Glycolysis inhibitor) |
 TEMPs/RAW264.7/in vivo | mild hypoxia /LPS | PDK1 | PDK1 significantly suppresses macrophage migration and systemic inflammation (35) | DCA(PDK inhibitor) |
 BMDMs/MoDMs/in vivo | LPS /IFNγ | itaconate | Itaconate exerts anti-inflammatory effects (48, 49, 51) |  |
 MoDMs/(U937/PMA cells)(46);  BMDMs/LPS-induced  model of peritonitis(43) | LPS/ TNFα/IFNγ (46) ; LPS (43) | ACLY | ACLY exerts pro-inflammatory effects (43, 46) | Radicicol (RAD) /hydroxycitrate (HCA)/SB-204990 (46) ; BMS 303141 (BMS) (43) |
 BMDMs | LPS | Succinate | Succinate exerts pro-inflammatory effects (53) |  |
 BMDMs/U937  /mice with antigen-induced arthritis | LPS/IFNγ | GPR91 | GPR91 senses extracellular succinate to enhance IL-1β production (55) | GPR91A1(GPR91 antagonist) |
Lipid synthesis | ||||
 BMDMs/mice with injection of LPS | LPS | SREBP-1a | SREBP-1a couples lipogenesis with the NLRP3 inflammasome activation (60) |  |
 BMDMs/PMs/J774A.1 /in vivo | LPS | FASN | Inhibition of FASN suppresses NLRP3 inflammasome activation (61) | C75 and cerulenin(FASN inhibitors) |
 BMDMs | IL-4 | FAS | FAS could be contributing to the fueling of FAO, which is essential for M2 activation (37) | C75(FAS inhibitor) |
Fatty acid oxidation | ||||
 BMDMs/primary human macrophages/a mouse model of S. pneumoniae lung infection | LPS/ATP/nigericin | NOX4 | NOX4-dependent fatty acid oxidation promotes NLRP3 inflammasome activation (63) | GKT137831 and VAS-2870(NOX4 inhibitors) |
Glutamine metabolism | ||||
 BMDMs | IL-4 | glutamine | Glutamine regulates M2 polarization (40, 71) |  |
 MoDMs/in vivo | IL-10 | Glutamine | Inhibition of GS skews macrophages toward an M1-like phenotype and Inhibits tumor metastasis (73) | methionine sulfoximine(GS inhibitor) |
Synthetase(GS) | ||||