Developmental regulation and localization of carnitine palmitoyltransferases ( CPT s) in rat brain

While the brain's high energy demands are largely met by glucose, brain is also equipped with the ability to oxidize fatty acids for energy and metabolism. The brain expresses the carnitine palmitoyltransferases ( CPT s) that mediate carnitine‐dependent entry of long‐chain acyl‐CoAs into the mitochondrial matrix for β‐oxidation – CPT 1a and CPT 2 located on the outer and inner mitochondrial membranes, respectively. Their developmental profile, regional distribution and activity as well as cell type expression remain unknown. We determined that brain CPT 1a RNA and total protein expression were unchanged throughout post‐natal development ( PND 0, PND 7, PND 14, PND 21 and PND 50); however, CPT 2 RNA peaked at PND 21 and remained unchanged through PND 50 in all regions studied (cortex, hippocampus, midbrain, and cerebellum). Both long‐chain acyl CoA dehydrogenase and medium acyl‐CoA dehydrogenase showed a similar developmental profile to CPT 2. Acylcarnitines, generated as a result of CPT 1a activity, significantly increased with age and peaked at PND 21 in all brain regions, concurrent with the increased expression of enzymes involved in mitochondrial β‐oxidation. The CPT system is highly enriched in vivo in hippocampus and cerebellum, relative to cortex and midbrain, and is exclusively present in astrocytes and neural progenitor cells, while absent in neurons, microglia, and oligodendrocytes. Using radiolabeled oleate, we demonstrate regional differences in brain fatty acid oxidation that may be blocked by the irreversible CPT 1a inhibitor etomoxir. This study contributes to the field of knowledge in brain cell‐specific metabolic pathways, which are important for understanding normal brain development and aging, as well as pathophysiology of neurological diseases. Read the Editorial Comment for this article on page 347.