Fuel and energy metabolism in fasting humans

Abstract

Fuel and energy homeostasis was examined in six male volunteers during a 60-h fast by using a combination of isotopic tracer techniques ([3-³H]glucose, [²H₅]glycerol, [1-¹⁴C]palmitate, and l-[1-¹³C]leucine) and indirect calorimetry. Plasma glucose concentration and hepatic glucose production decreased by 30% with fasting (5.2 ± 0.1 to 3.8 ± 0.2 mmol/L and 11.8 ± 0.5 to 8.2 ± 0.6 µmol·kg⁻¹·min⁻¹, respectively, both P < 0.001) and glucose oxidation declined ≈85% (P < 0.01). Lipolysis and primary (intraadipocyte) free fatty acid (FFA) reesterification increased 2.5-fold (1.7 ± 0.2 to 4.2 ± 0.2 µmol·kg⁻¹·min⁻¹ and 1.5 ± 0.4 to 4.2 ± 0.8 µ mol·kg⁻¹·min⁻¹, respectively, both P < 0.05). This provided substrate for the increase in fat oxidation (from 2.7 ± 0.3 to 4.3 ± 0.1 µ mol·kg⁻¹·min⁻¹, P < 0.01), which contributed ≈75% of resting energy requirements after the 60-h fast and increased the supply of glycerol for gluconeogenesis. Proteolysis and protein oxidation increased ≈50% during fasting (P < 0.01 and P < 0.05, respectively). We conclude that the increase in FFA reesterification with fasting modulates FFA availability for oxidation and maximizes release of glycerol from triglyceride for gluconeogenesis.