Fuel and energy metabolism in fasting humans

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 mumol.kg-1.min-1, respectively, both P < 0.001) and glucose oxidation declined approximately 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 mumol.kg-1.min-1 and 1.5 +/- 0.4 to 4.2 +/- 0.8 mumol.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 mumol.kg-1.min-1, P < 0.01), which contributed approximately 75% of resting energy requirements after the 60-h fast and increased the supply of glycerol for gluconeogenesis. Proteolysis and protein oxidation increased approximately 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.