Continuous contractile activity of the heart is essential and the required energy is mostly provided by
fatty acid (FA) oxidation. Myocardial
lipid accumulation can lead to pathological responses, however the underlying mechanisms remain elusive. The role of
myoglobin in
dioxygen binding in cardiomyocytes and oxidative skeletal muscle has widely been appreciated. Our recent work established
myoglobin as a protector of cardiac function in
hypoxia and disease states. We here unravel a novel role of cardiac
myoglobin in governing FA metabolism to ensure the physiological energy production through β-oxidation, preventing myocardial
lipid accumulation and preserving cardiac functions. In vivo1H magnetic resonance spectroscopy unveils a 3-fold higher deposition of
lipids in mouse hearts lacking
myoglobin, which was associated with depressed cardiac function compared to wild-type hearts as assessed by echocardiography. Mass spectrometry reveals a marked increase in tissue
triglycerides with preferential incorporation of palmitic and
oleic acids.
Phospholipid levels as well as the metabolome, transcriptome and
proteome related to FA metabolism tend to be unaffected by
myoglobin ablation. Our results reveal a physiological role of
myoglobin in FA metabolism with the
lipid accumulation-suppressing effects of
myoglobin preventing cardiac lipotoxicity.