rFVIIIFc-treated macrophages exhibit elevated mitochondrial activity, bioenergy, and glutathione production. Macrophages were treated with IgG1, rFVIII, or rFVIIIFc for 24 hours. Significantly elevated levels of mitochondrial transmembrane potential (A) and active mitochondria staining (B) were measured from lysates of the rFVIIIFc-treated cells, compared with other treatments (n = 3). None of the treatments altered the total mitochondrial mass (C) indicating that rFVIIIFc-educated macrophages specifically upregulate their oxidative phosphorylation capacity (n = 3). Significantly elevated production of ATP (D, n = 5) and GSH (E, n = 3; F, n = 5) of rFVIIIFc-treated macrophages was measured compared with other treatments. (G) Endogenous PPARγ ligands 13-hydroxyoctadecadienoic acid (13-HODE) and 9-HODE were produced by rFVIIIFc-treated macrophages (n = 3). (H) Metabolism status of rFVIIIFc-treated macrophages is illustrated. Mean ± SE; *P ≤ .05.