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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

From: Metabolic reprogramming in macrophage responses

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)  
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
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 /
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)
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);
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)  
/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)