Abstract
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 β-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 μM which corresponds to the total concentration of LC acylcarnitines in the brain. Maximal respiration with octanoylcarnitine was reached at 20 μM, 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.
Original language | English |
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Article number | 167544 |
Journal | Biochimica et Biophysica Acta - Molecular Basis of Disease |
Volume | 1871 |
Issue number | 1 |
DOIs | |
Publication status | Published - Jan 2025 |
Keywords*
- Acylcarnitines
- Beta-oxidation
- Brain
- Fatty acid oxidation
- Mitochondrial function
- Nervous system
- Respirometry
Field of Science*
- 3.1 Basic medicine
- 1.6 Biological sciences
- 1.4 Chemical sciences
Publication Type*
- 1.1. Scientific article indexed in Web of Science and/or Scopus database