| Cardoso LHD, Cecatto C, Ozola M, Korzh S, Zvejniece L, Gukalova B, Doerrier C, Dambrova M, Makrecka-Kuka M, Gnaiger E, Liepinsh E (2024) Fatty acid Ξ²-oxidation in brain mitochondria: Insights from high-resolution respirometry in mouse, rat and Drosophila brain, ischemia and aging models. MitoFit Preprints 2023.10. https://doi.org/10.26124/mitofit:2023-0010.v2 |
Β» MitoFit Preprints 2023.10.v2.
Cardoso Luiza HD, Cecatto Cristiane, Ozola Melita, Korzh Stanislava, Zvejniece Liga, Gukalova Baiba, Doerrier Carolina, Dambrova Maija, Makrecka-Kuka Marina, Gnaiger Erich, Liepinsh Edgars (2024) MitoFit Prep
Abstract:
- Version 2 (v2) 2024-07-30
- Version 1 (v1) 2023-11-22 - Β»Link to all versionsΒ«
Glucose is the main energy source of the brain, yet recent studies demonstrate that fatty acid oxidation (FAO) plays a relevant role in the pathogenesis of central nervous system disorders. We evaluated FAO in brain mitochondria under physiological conditions, in the aging brain, and after stroke. Using high-resolution respirometry we compared medium-chain (MC, octanoylcarnitine) and long-chain (LC, palmitoylcarnitine) acylcarnitines as substrates of Ξ²-oxidation in the brain. The protocols developed avoid FAO overestimation by malate-linked anaplerotic activity in brain mitochondria. The capacity of FA oxidative phosphorylation (F-OXPHOS) with palmitoylcarnitine was up to 4 times higher than respiration with octanoylcarnitine. The optimal concentration of palmitoylcarnitine was 10 Β΅M which corresponds to the total concentration of LC acylcarnitines in the brain. Maximal respiration with octanoylcarnitine was reached at 20 Β΅M, however, this concentration exceeds MC acylcarnitine concentrations in the brain 15 times. F-OXPHOS capacity was highest in mouse cerebellum, intermediate in cortex, prefrontal cortex, and hypothalamus, and hardly detectable in hippocampus. F-OXPHOS capacity was 2-fold lower and concentrations of LC acylcarnitines were 2-fold higher in brain of aged rats. A similar trend was observed in the rat model of endothelin-1-induced stroke, but reduction of OXPHOS capacity was not limited to FAO. In conclusion, although FAO is not a dominant pathway in brain bioenergetics, it deserves specific attention in studies of brain metabolism.
β’ Keywords: brain; nervous system; mitochondrial function; fatty acid oxidation; beta-oxidation; acylcarnitines; respirometry. β’ Bioblast editor: Cardoso LHD β’ O2k-Network Lab: AT Innsbruck Oroboros, LV Riga Liepins E
ORCID:
Luiza H. D. Cardoso, Cristiane Cecatto, Melita Ozola, Stanislava Korzh, Liga Zvejniece, Baiba Gukalova, Carolina Doerrier,
Maija Dambrova, Marina Makrecka-Kuka, Erich Gnaiger, Edgars Liepinsh
Labels: MiParea: Respiration
Pathology: Aging;senescence
Stress:Ischemia-reperfusion
Organism: Mouse, Rat, Drosophila
Tissue;cell: Heart, Nervous system, Kidney
Preparation: Homogenate
Regulation: Substrate, Fatty acid Coupling state: OXPHOS, ET Pathway: F, N, S, Gp
FAT4BRAIN, Publication:FAT4BRAIN
