FIGURE 3.

TLR4-induced metabolic switching of glucose and fatty acid metabolism requires Nampt-dependent NAD⁺ generation. NAD⁺ was depleted by treating cells for 24 h with FK866, and TLR4 was stimulated with LPS for another 24 h. A, schematic of epigenetic gene-selective reprogramming and bioenergy shifts during the acute inflammatory response. B, dynamic changes of cellular NAD⁺ and NADH during TLR4 activation. C, dynamic changes of NAD⁺/NADH ratio during TLR4 activation. D, FK866 reduces mitochondrial glucose oxidation in quiescent cells and restrains its increase at 24 h. E, FK866 inhibits LPS-induced increase in fatty acid oxidation at 24 h. F, FK866 alters key glucose and fatty acid metabolism regulators: PDHK1, PDHA1, p-PDHA1-Ser-232, and CPT-1. Bar graphs represent mean ± S.E. of one of two independent experiments. FK, FK866; med, medium.