Question

Is fatty acid an effective energy source in the central nervous system?

Answer 1

Answer: No, fatty acid is not an effective energy source in the central nervous system.

(1) ATP generation linked to -oxidation of fatty acids demands more oxygen than glucose, thereby enhancing the risk for neurons to become hypoxic

(2) -oxidation of fatty acids generates superoxide, which, taken together with the poor anti-oxidative defense in neurons, causes severe oxidative stress

(3) the rate of ATP generation based on adipose tissue-derived fatty acids is slower than that using blood glucose as fuel.

Thus, in periods of extended continuous and rapid neuronal firing, fatty acid oxidation cannot guarantee rapid ATP generation in neurons.

We conjecture that the disadvantages connected with using fatty acids as fuel have created evolutionary pressure on lowering the expression of the -oxidation enzyme equipment in brain mitochondria to avoid extensive fatty acid oxidation and to favor glucose oxidation in brain.