Changing the paradigm for myoglobin: a novel link between lipids and myoglobin.

Myoglobin (Mb) is an oxygen-binding muscular hemeprotein regulated via Ca(2+)-signaling pathways involving calcineurin (CN), with Mb increases attributed to hypoxia, exercise, and nitric oxide. Here, we show a link between lipid supplementation and increased Mb in skeletal muscle. C2C12 cells were cultured in normoxia or hypoxia with glucose or 5% lipid. Mb assays revealed that lipid cohorts had higher Mb than control cohorts in both normoxia and hypoxia, whereas Mb Western blots showed lipid cohorts having higher Mb than control cohorts exclusively under hypoxia. Normoxic cells were compared with soleus tissue from normoxic rats fed high-fat diets; whereas tissue sample cohorts showed no difference in CO-binding Mb, fat-fed rats showed increases in total Mb protein (similar to hypoxic cells), suggesting increases in modified Mb. Moreover, Mb increases did not parallel CN increases but did, however, parallel oxidative stress marker augmentation. Addition of antioxidant prevented Mb increases in lipid-supplemented normoxic cells and mitigated Mb increases in lipid-supplemented hypoxic cells, suggesting a pathway for Mb regulation through redox signaling independent of CN.