Figure 6.

Glycolysis and NAD⁺ Salvage Drive Pro-Inflammation in Slc37a2^−/− Macrophages

(A) Schematic representation of glycolysis. The targeting sites of the pharmaceutical inhibitors are indicated.

(B and C) TNF secretion from WT and Slc37a2^−/− BMDMs pretreated with hexokinase inhibitor 2-deoxy-D-glucose (2-DG; 10 mM), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibitor iodoacetate (200 μM), lactate dehydrogenase inhibitor sodium oxamate (40 mM), glucose-6-phosphate dehydrogenase (G6PDH) inhibitor dehydroepiandrosterone (DHEA) (200 μM), followed by 100 ng/mL LPS for 6 h.

(D) Schematic representation of glycolysis and NAD biosynthetic pathways.

(E–G) The relative level of metabolites in NAD⁺de novo synthesis and salvage pathways in WT and Slc37a2^−/− macrophages treated with or without 100 ng/mL LPS for 3 h, assessed by unbiased metabolomics.

(H) Expression of genes involved in NAD⁺de novo synthesis and salvage pathways in resting WT and Slc37a2^−/− macrophages, assessed by RNA-seq.

(I) TNF secretion from WT and Slc37a2^−/− BMDMs pretreated with nicotinamide phosphoribosyltransferase (NAMPT) inhibitor FK866 (50 nM), followed by 100 ng/mL LPS for 6 h.

Data are representative of two independent experiments with four samples per group (mean ± SEM). ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.001, two-tailed Student's t test (H) or two-way ANOVA with post hoc Tukey's multiple comparisons test (B, C, E, F, G, and I).