title: Tissue-specific changes in fatty acid oxidation in hypoxic heart and skeletal muscle.
abstract: Exposure to hypobaric hypoxia is sufficient to decrease cardiac PCr/ATP and alters skeletal muscle energetics in humans. Cellular mechanisms underlying the different metabolic responses of these tissues and the time-dependent nature of these changes are currently unknown, but altered substrate utilization and mitochondrial function may be a contributory factor. We therefore sought to investigate the effects of acute (1 day) and more sustained (7 days) hypoxia (13% O₂) on the transcription factor peroxisome proliferator-activated receptor α (PPARα) and its targets in mouse cardiac and skeletal muscle. In the heart, PPARα expression was 40% higher than in normoxia after 1 and 7 days of hypoxia. Activities of carnitine palmitoyltransferase (CPT) I and β-hydroxyacyl-CoA dehydrogenase (HOAD) were 75% and 35% lower, respectively, after 1 day of hypoxia, returning to normoxic levels after 7 days. Oxidative phosphorylation respiration rates using palmitoyl-carnitine followed a similar pattern, while respiration using pyruvate decreased. In skeletal muscle, PPARα expression and CPT I activity were 20% and 65% lower, respectively, after 1 day of hypoxia, remaining at this level after 7 days with no change in HOAD activity. Oxidative phosphorylation respiration rates using palmitoyl-carnitine were lower in skeletal muscle throughout hypoxia, while respiration using pyruvate remained unchanged. The rate of CO₂ production from palmitate oxidation was significantly lower in both tissues throughout hypoxia. Thus cardiac muscle may remain reliant on fatty acids during sustained hypoxia, while skeletal muscle decreases fatty acid oxidation and maintains pyruvate oxidation.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge, United Kingdom. andrea.morash@utas.edu.au
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Morash
authors.forename: Aleksandra O
authors.initials: AO
authors.lastname: Kotwica
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murray
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D010084:Oxidation-Reduction; D019289:Pyruvic Acid / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D019289:Pyruvic Acid
keywords: fatty acids; heart; hypoxia; metabolism; mitochondrial respiration