Lipid stimulates myoglobin expression in skeletal muscle cells

Abstract

Myoglobin (Mb) is an oxygen‐binding hemoprotein generally localized in muscle tissue, where it functions as an oxygen store, nitric oxide (NO) scavenger, and reactive oxygen species (ROS) scavenger. Regulation of Mb is thought to occur through a calcium‐dependent signaling pathway involving calcineurin and nuclear factor of activated t‐cells (NFAT), with increases in Mb expression attributed to factors such as hypoxic exercise and NO. Here, we show a link between lipid supplementation and Mb expression in C2C12 cells. Specifically, C2C12 cells were cultured in normoxic (21% O2) or hypoxic (0.5% O2) conditions in either standard, high glucose media or a 5% lipid‐supplemented media. Mb assays and western blots revealed hypoxic cells differentiated in high fat media had significantly higher Mb content than high glucose hypoxic cells and both lines of normoxic cells. Citrate synthase activity (i.e. aerobic activity), however, significantly decreased in hypoxic, high fat cells. Further, normoxic cells were also compared to tissue from rats fed a high fat diet. Interestingly, both normoxic high fat conditions showed no change in Mb activity (per Mb assay) relative to the high glucose conditions, but did show an increase in total Mb protein (per western blot), suggesting an increase in non‐functional Mb. These results present a novel role for lipids in stimulating Mb, possibly to fill a niche beyond oxygen storage.