Figure 6.

Impact of hypoxia-inducible factor-1α (HIF1α) deficiency on lipid metabolism and MYC signaling pathways. A:Lyz2^cre/cre and Hif1α^fl/fl:Lyz2^cre/cre mice bone marrow–derived macrophages (BMDMs) were stimulated with 100 ng/mL lipopolysaccharide (LPS) for 6 hours. Indicated tricarboxylic acid cycle (TCA) metabolites were quantified by liquid chromatography–mass spectrometry–based targeted metabolomics analyses. B: The oxygen consumption rate (OCR) of LPS-induced Lyz2^cre/cre and Hif1α^fl/fl:Lyz2^cre/cre mice BMDMs. C–E:Lyz2^cre/cre and Hif1α^fl/fl:Lyz2^cre/cre mice BMDMs were stimulated with 100 ng/mL LPS for 6 hours. C–E: Total RNA extracts were analyzed for expression of MYC targets (Ddx18, Hspe1, and Xrcc6; C), oxidative phosphorylation (Ndufs8, Atp6v1f, and Uqcrfs1; D), and TCA (Idh2, Mdh1, and Suclg2; E) gene targets by RT-qPCR. F: Total RNA samples from Lyz2^cre/cre and Hif1α^fl/fl:Lyz2^cre/cre mice control and stenotic carotid artery macrophages were analyzed for expression of indicated MYC targets, oxidative phosphorylation, and TCA genes by RT-qPCR. Data were analyzed by analysis of variance, followed by Bonferroni post-testing. Values are reported as means ± SD (A–F). n = 3 (A and B); n = 4 (C–E); n = 6 (F). ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001. Ant, antimycin A; FCCP, fluorocarbonyl cyanide phenylhydrazone; Oligo, oligomycin; Rot, rotenone.