Glutamine blocks lipolysis and ketogenesis of fasting

Several in vivo studies have indirectly suggested a relationship between blood glutamine and ketonemia. The present study was designed to characterize the role glutamine plays in regulating lipolysis and ketogenesis during fasting in vivo. Twelve dogs had catheters implanted in the hepatic and portal veins (V) and in the femoral artery (A) 17-21 days before study. The animals were fasted for 4 days. After a 120-min rest and 40-min basal periods, 6 dogs received an infusion of L-glutamine at 6 μmol·kg^-1·min^-1 and 6 received saline and acted as controls. Hepatic and splanchnic balances (μmol·kg^-1·min^-1) were estimated by A-V differences multiplied by blood flow determined by indocyanine green. Fasting was associated with a compensated (no change in pH) mild metabolic acidosis but no change in plasma insulin and glucagon or blood glutamine. L-Glutamine infusion increased blood glutamine by 20% but decreased arterial free fatty acids (FFA, from 1,054 ± 47 to 850 ± 43 μmol/l, P < 0.01), β-hydroxybutyrate (β-OHB, from 136 ± 15 to 66 ± 8 μmol/l, P < 0.01), acetoacetate (AcAc, from 168 ± 26 to 86 ± 21 μmol/l, P < 0.01), and glycerol (from 90 ± 4 to 65 ± 5 μmol/l, P < 0.01). It also decreased hepatic uptake of glycerol (from 2.5 ± 0.5 to 0.8 ± 0.3 μmol·kg^-1·min^-1, P < 0.01) and FFA (from 4.3 ± 0.7 to 1.4 ± 0.2 μmol·kg^-1·min^-1, P < 0.01) and release of β-OHB (from 4.2 ± 1.2 to 1.8 ± 0.3 μmol·kg^-1·min^-1, P < 0.01) and AcAc (from 3.0 ± 0.5 to 1.5 ± 0.3 μmol·kg^-1·min^-1, P < 0.01). The results indicate that a physiological increment in blood glutamine inhibits lipolysis and possibly ketogenesis.