During prolonged starvation (>3 weeks), the brain adapts to use which fuel, thereby reducing protein catabolism?

• A Free fatty acids transported across the blood-brain barrier
• B Glycerol released from adipose lipolysis
• C Branched-chain amino acids directly oxidised by neurons
• D Ketone bodies (beta-hydroxybutyrate and acetoacetate) ✓

Explanation

After 3 weeks of starvation the brain derives up to 75% of its energy from ketone bodies produced by hepatic ketogenesis from fatty acids; this reduces gluconeogenic demand, sparing muscle protein. Free fatty acids cannot cross the blood-brain barrier in significant amounts. Glycerol is a minor gluconeogenic substrate. Branched-chain amino acids are metabolised by muscle, not neurons.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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