Table 1.

Macrophage immunometabolism and atherosclerosis

Metabolite/ regulating step	Cellular source	Possible stimuli in lesion	Effect on macrophages	Effect on atherosclerosis
Intracellular
Glucose/SLC2A1	MΦ	Apoptotic cell, TLR4 ligands hypoxia	Altered inflammation and increased efferocytosis21, 50, 124	Prevention of necrotic cores* (mouse)50, 124
Lactate	MΦ	TLR4 ligands, hypoxia, oxLDL	Resolution of inflammation16	Unknown
Non-oxPPP/SHPK	MΦ	IL-4	Suppression of inflammatory activation17	Unknown
Succinate	MΦ	TLR4 ligands	IL-1β production	Unknown
Citrate	MΦ	TLR4 ligands	TNF-α translation37	Unknown
α-ketoglutarate	MΦ	TLR4 ligands	LPS tolerance39	Unknown
Itaconate/ACOD1	MΦ	TLR4 ligands	Resolution of inflammation and LPS tolerance41	Unknown
Oxaloacetate/citrate	MΦ	oxPAPC	IL-1β production64	Promotes atherosclerosis^ (mouse)64
Arginine/Arg1	MΦ	IL-4	Promotes foam cell formation143	No effect on atherosclerosis§ (mouse)143
Arginine/iNOS	MΦ	TLR4 ligands	Suppresses IL-12 production144	Promotes lesion area§ (mouse)145
Serine	MΦ	TLR4 ligands	IL-1β production67, 68	Unknown
Acyl-CoA/ACSL1	MΦ	TLR4 ligands, oxLDL	Promotes inflammatory activation86, 89	Promotes lesion initiation* (diabetic mouse)86
Fatty acids/FAS	MΦ	oxysterols	Promotes lipid loading146	Promotes atherosclerosis* (mouse)146
Fatty acids/FABP4	MΦ	oxLDL	Promotes inflammatory activation and CE accumulation84	Promotes lesion area§ (mouse)84
Mitochondrial ROS	MΦ	oxLDL	Promotes CCL2, IL-1β, and IL-6 production55, 78	Promotes lesion initiation* (mouse)78
				Associated with coronary artery disease (humans)55
Intracellular
Lactate/SLC16A1	MΦ cargo	Apoptotic cell	Resolution of inflammation50	Unknown
	Lesional cells	Inflammation, hypoxia
Succinate/ SUCNR1	Lesional cells	TLR4 ligands	IL-1β28	Unknown
Arginine/putrescine	MΦ cargo	Apoptotic cell	Continual efferocytosis125	Promotes lesion regression (mouse)125

CE, cholesteryl ester; HK1, hexokinase 1; MΦ, macrophage; non-oxPPP, non-oxidative phase of pentose phosphate pathway; SLC2A1, GLUT1

^*Myeloid cell targeted deletion or overexpression

^§Hematopoietic deletion (bone marrow transplant)

^{^}Indirect evidence