Makrecka-Kuka 2018 MiP2018
The brain tissues have a high energy demand that is almost exclusively satisfied by metabolizing glucose. Recent studies have demonstrated that also fatty acids are utilized by brain mitochondria. However, the role of fatty acid oxidation (FAO) in brain tissues is still unclear. The aim of the present study was to evaluate the fatty acid oxidation in brain under physiological and pathological conditions.
Mitochondrial respiration was measured using High-Resolution Fluoespirometry in brain tissue homogenates. The measurements were performed at saturated ADP state using palmitoylcarnitine (PC) or octanoylcarnitine (OC) as substrates. The FAO was evaluated in brain tissues of adult (8 months) and old (20 months) Wistar male rats, as well as in tissues after endothelin-1 (ET-1) induced stroke. In addition, measurements were done using high fat diet-induced insulin resistance and LPS-induced endotoxic shock experimental mice models.
The measurements in control mice tissues demonstrated that FA-dependent O2 flux is higher using PC than OC. Moreover, PC, but not OC, inhibits pyruvate metabolism in brain. The PC-dependent O2 flux was 2.3 times lower in old rat brain compared to adult rat group. In ET-1 induced experimental model of stroke we observed 31% and 66% decrease in PC-dependent O2 flux 2h and 24h post- ET-1 injection in affected brain area compared to sham control. The high-fat diet for 18 weeks resulted in a 56% reduction of PC-dependent O2 flux in mice brain. Similarly, the PC-dependent O2 flux was by 52% lower in LPS-treated mice compared to control group.
Taking into account FAO biochemical pathway and obtained results, the measurements using PC are more straight-forward to characterize FAO in mitochondria. All studied conditions induced an inhibition of FAO in brain, indicating that FAO and availability of FA metabolites could regulate physiological process as well as play a significant role in the development of neurological disorders. Targeting FAO and availability of FA metabolites provide a novel therapeutic approach for treatment of neuropathological states.
- Makrecka-Kuka Marina(1), Doerrier C(2), Korzh S(1), Zvejniece L(1), Gnaiger E(2,3), Dambrova M(1), Liepinsh E(1)
- Latvian Inst Organic Synthesis, Riga, Latvia. - firstname.lastname@example.org
- Oroboros Instruments, Innsbruck, Austria
- Medical Univ Innsbruck, Austria
- This study was supported by “Post-doctoral Research Aid” programme project Nr.184.108.40.206/VIAA/1/16/246. Contribution to COST Action MitoEAGLE.
Labels: MiParea: Exercise physiology;nutrition;life style Pathology: Aging;senescence, Neurodegenerative, Sepsis Stress:Ischemia-reperfusion Organism: Mouse, Rat Tissue;cell: Nervous system Preparation: Homogenate
Regulation: Fatty acid Coupling state: OXPHOS Pathway: F