During prolonged starvation (>7 days), the brain significantly shifts its fuel utilization. Which metabolic adaptation allows the brain to reduce its dependence on glucose?
- A Upregulation of monocarboxylate transporters allowing ketone bodies (beta-hydroxybutyrate and acetoacetate) to become the predominant fuel ✓
- B Increased glycerol utilisation as direct neuronal fuel
- C Activation of glycogen phosphorylase in astrocytes to release glucose
- D Increased fatty acid oxidation in neurons, replacing glucose entirely
Explanation
After 7–10 days of starvation, plasma ketone bodies rise substantially (ketonaemia); the brain upregulates monocarboxylate transporters (MCT1/MCT2) on blood-brain barrier and neurons, enabling uptake of beta-hydroxybutyrate and acetoacetate. Ketone bodies can supply up to 60–70% of brain energy needs during prolonged starvation, reducing glucose requirements from ~140 g/day to ~40 g/day and thereby sparing muscle protein from gluconeogenic consumption. Neurons cannot directly oxidize fatty acids (long-chain fatty acids do not cross the blood-brain barrier efficiently), but ketone bodies, being water-soluble, can.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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