title: Long-chain acylcarnitine content determines the pattern of energy metabolism in cardiac mitochondria.
abstract: In the heart, a nutritional state (fed or fasted) is characterized by a unique energy metabolism pattern determined by the availability of substrates. Increased availability of acylcarnitines has been associated with decreased glucose utilization; however, the effects of long-chain acylcarnitines on glucose metabolism have not been previously studied. We tested how changes in long-chain acylcarnitine content regulate the metabolism of glucose and long-chain fatty acids in cardiac mitochondria in fed and fasted states. We examined the concentrations of metabolic intermediates in plasma and cardiac tissues under fed and fasted states. The effects of substrate availability and their competition for energy production at the mitochondrial level were studied in isolated rat cardiac mitochondria. The availability of long-chain acylcarnitines in plasma reflected their content in cardiac tissue in the fed and fasted states, and acylcarnitine content in the heart was fivefold higher in fasted state compared to the fed state. In substrate competition experiments, pyruvate and fatty acid metabolites effectively competed for the energy production pathway; however, only the physiological content of acylcarnitine significantly reduced pyruvate and lactate oxidation in mitochondria. The increased availability of long-chain acylcarnitine significantly reduced glucose utilization in isolated rat heart model and in vivo. Our results demonstrate that changes in long-chain acylcarnitine contents could orchestrate the interplay between the metabolism of pyruvate-lactate and long-chain fatty acids, and thus determine the pattern of energy metabolism in cardiac mitochondria.
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga, 1006, Latvia, makrecka@biomed.lu.lv.
authors.forename: Marina
authors.initials: M
authors.lastname: Makrecka
authors.forename: Janis
authors.initials: J
authors.lastname: Kuka
authors.forename: Kristine
authors.initials: K
authors.lastname: Volska
authors.forename: Unigunde
authors.initials: U
authors.lastname: Antone
authors.forename: Eduards
authors.initials: E
authors.lastname: Sevostjanovs
authors.forename: Helena
authors.initials: H
authors.lastname: Cirule
authors.forename: Solveiga
authors.initials: S
authors.lastname: Grinberga
authors.forename: Osvalds
authors.initials: O
authors.lastname: Pugovics
authors.forename: Maija
authors.initials: M
authors.lastname: Dambrova
authors.forename: Edgars
authors.initials: E
authors.lastname: Liepinsh
mesh_terms: D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism; D004734:Energy Metabolism; D005215:Fasting; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008929:Mitochondria, Heart / Q000502:physiology*; D023421:Models, Animal; D010172:Palmitoylcarnitine / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005227:Fatty Acids; C116917:acylcarnitine; D010172:Palmitoylcarnitine; D005947:Glucose; D002331:Carnitine