Fatty Acids in Energy Metabolism of the Central Nervous System

Abstract

In this review, we analyze the current hypotheses regarding energy metabolism in the neurons and astroglia. Recently, it was shown that up to 20% of the total brain's energy is provided by mitochondrial oxidation of fatty acids. However, the existing hypotheses consider glucose, or its derivative lactate, as the only main energy substrate for the brain. Astroglia metabolically supports the neurons by providing lactate as a substrate for neuronal mitochondria. In addition, a significant amount of neuromediators, glutamate and GABA, is transported into neurons and also serves as substrates for mitochondria. Thus, neuronal mitochondria may simultaneously oxidize several substrates. Astrocytes have to replenish the pool of neuromediators by synthesis de novo, which requires large amounts of energy. In this review, we made an attempt to reconcile β-oxidation of fatty acids by astrocytic mitochondria with the existing hypothesis on regulation of aerobic glycolysis. We suggest that, under condition of neuronal excitation, both metabolic pathways may exist simultaneously. We provide experimental evidence that isolated neuronal mitochondria may oxidize palmitoyl carnitine in the presence of other mitochondrial substrates. We also suggest that variations in the brain mitochondrial metabolic phenotype may be associated with different mtDNA haplogroups.

Functional Expression of Organic Ion Transporters in Astrocytes and Their Potential as a Drug Target in the Treatment of Central Nervous System Diseases

“…23) The presence of OCTN2 in astrocytes seems reasonable, since astrocytes require substantial amounts of energy to fulfill their roles. Panov et al 42) have hypothesized that, in line with the fact that perisynaptic processes of astrocytes hold large numbers of mitrochondria, 43) fatty acid β-oxidation is the preferable process for acetyl-CoA production, by which astrocytes accomplish large-scale production of lactate and ATP at the same time. And in fact, fatty acid oxidation in astrocytes has been proven to date.…”

Are astrocytes executive cells within the central nervous system?

“…Synaptic activity is modulated by astrocytes, which enhance or diminish the synaptic strength by delivering gliotransmitters and transmitter transporters 14 while providing neurons with glucose and O 2 and adapting the blood flow to their requirements, thus establishing a very close relationship with them. Moreover, astrocytes are the source of not only glucose and O 2 , but also of other metabolites such as lactate, fatty acids and trophic factors that sustain neuronal health 15 .…”

Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities

“…2) [33,62]. Ketone bodies are formed in the liver from fatty acid oxidation and are transported to the brain [31,62,63].…”

“…Mitochondrial dysfunction and endoplasmic reticulum (ER) stress activate apoptotic pathways that lead to neuronal loss and continuation of the AD pathology spectrum. GLUT = glucose transporter; MCT = monocarboxylate transporter; PDH = pyruvate dehydrogenase; SCOT = succinyl-coenzyme A:3-ketoacid CoA transferase ketolytic enzymes such as succinyl-coenzyme A (CoA):3-ketoacid CoA transferase instead of pyruvate dehydrogenase (PDH) to produce acetyl-CoA, which condenses with oxaloacetate and enters the citric acid cycle for energy production [31,62]. Several therapeutic strategies aim to enhance brain bioenergetics through supplementation of ketone bodies, including acetoacetate and β-hydroxybutyrate [64,65], or dietary induction of ketogenesis [56].…”