title: A novel physiological role for cardiac myoglobin in lipid metabolism.
abstract: 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.
authors.affiliation: University Hospital Essen, Medical Faculty, West German Heart and Vascular Center, Department of Cardiology and Department of Angiology, Hufelandstr. 55, 45147 Essen, Germany.
authors.forename: Ulrike B
authors.initials: UB
authors.lastname: Hendgen-Cotta
authors.affiliation: University Hospital Essen, Medical Faculty, West German Heart and Vascular Center, Department of Cardiology and Department of Angiology, Hufelandstr. 55, 45147 Essen, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Esfeld
authors.affiliation: Leibniz-Institut für Analytische Wissenschaften-ISAS e.V. Otto-Hahn-Str. 6b, 44227 Dortmund, Germany.
authors.forename: Cristina
authors.initials: C
authors.lastname: Coman
authors.affiliation: Leibniz-Institut für Analytische Wissenschaften-ISAS e.V. Otto-Hahn-Str. 6b, 44227 Dortmund, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Ahrends
authors.affiliation: University Hospital Essen, Institute of Cell Biology, Medical Faculty, Virchowstr. 173, 45122 Essen, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Klein-Hitpass
authors.affiliation: University Hospital Düsseldorf, Department of Molecular Cardiology, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Flögel
authors.affiliation: University Hospital Essen, Medical Faculty, West German Heart and Vascular Center, Department of Cardiology and Department of Angiology, Hufelandstr. 55, 45147 Essen, Germany.
authors.forename: Tienush
authors.initials: T
authors.lastname: Rassaf
authors.affiliation: University Hospital Essen, Medical Faculty, West German Heart and Vascular Center, Department of Cardiology and Department of Angiology, Hufelandstr. 55, 45147 Essen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Totzeck
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism*; D008055:Lipids / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000737:chemistry; D009211:Myoglobin / Q000172:deficiency / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D008055:Lipids; D009211:Myoglobin