Cardoso 2024 MitoFit FAO

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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€” Published 2024-10-17 BBA Mol Basis Dis (2025)

Β» MitoFit Preprints 2023.10.v2.

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Fatty acid Ξ²-oxidation in brain mitochondria: Insights from high-resolution respirometry in mouse, rat and Drosophila brain, ischemia and aging models

MitoFit Preprints (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: ORCID.png Luiza H. D. Cardoso, ORCID.png Cristiane Cecatto, ORCID.png Melita Ozola, ORCID.png Stanislava Korzh, ORCID.png Liga Zvejniece, ORCID.png Baiba Gukalova, ORCID.png Carolina Doerrier, ORCID.png Maija Dambrova, ORCID.png Marina Makrecka-Kuka, ORCID.png Erich Gnaiger, ORCID.png 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 


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