Systemic pH modifies ketone body production rates and lipolysis in humans

To investigate whether changes in systemic pH influence ketone body production or utilization, total ketone body (TK) kinetics were measured with [3-14C]acetoacetate and D-beta-[1,3-13C2]hydroxybutyrate tracers in overnight fasted subjects during metabolic alkalosis (NaHCO3 infusion) or acidosis [NH4Cl ingestion or arginine (Arg)-HCl infusion]. Somatostatin, with insulin, glucagon, and growth hormone replacement, was infused in all studies. Blood pH and HCO3- (mM) increased from baseline (0-30 min) to 180-210 min by 0.08 +/- 0.02 and 7 +/- 1 with NaHCO3 and decreased by 0.08 +/- 0.2 and 7 +/- 1 or 5 +/- 1 with NH4Cl or Arg-HCl (all P less than 0.005). Over this period blood TK (microM) differed between the NaHCO3 (+198 +/- 65) and both NH4Cl (-90 +/- 53) and Arg-HCl (-154 +/- 55) (P less than 0.05). These changes resulted from parallel alterations in TK production rate of appearance (Ra TK, mumol.kg-1.min-1), because changes from baseline in Ra 14C TK also differed between NaHCO3 (+1.9 +/- 0.8) and NH4Cl (-1.0 +/- 0.6) and Arg-HCl (-2.0 +/- 0.5) (P less than 0.05). Ra TK calculated with single- or dual-tracer techniques were similar. Blood free fatty acids (FFA) increased with NaHCO3, and FFA and glycerol decreased with NH4Cl and Arg-HCl, suggesting that FFA availability mediated the pH effects on hepatic ketogenesis. These results demonstrate that modest changes in systemic pH modify FFA availability and TK production rates.