Lipolysis and lipid oxidation in cirrhosis and after liver transplantation

Abstract

On the basis of the finding that plasma glycerol concentration is not controlled by clearance in healthy humans, it has been proposed that elevated plasma free fatty acid (FFA) and glycerol concentrations in cirrhotic subjects are caused by accelerated lipolysis. This proposal has not been validated. We infused 10 volunteers, 10 cirrhotic subjects, and 10 patients after orthotopic liver transplantation (OLT) with [1-13C]palmitate and [2H5]glycerol to compare fluxes (Ra) and FFA oxidation. Cirrhotic subjects had higher plasma palmitate (52%) and glycerol (33%) concentrations than controls. Palmitate Ra was faster (1.45 ± 0.18 vs. 0.85 ± 0.17 μmol ⋅ kg−1 ⋅ min−1) but glycerol Ra and clearance slower (1.20 ± 0.09 vs. 1.90 ± 0.24 μmol ⋅ kg−1 ⋅ min−1and 21.2 ± 1.2 vs. 44.7 ± 4.9 ml ⋅ kg− ⋅ h−1, respectively) than in controls. After OLT, plasma palmitate and glycerol concentrations and palmitate Ra did not differ, but glycerol Ra (1.16 ± 0.11 μmol ⋅ kg−1 ⋅ min−1) and clearance (26.7 ± 2.4 ml ⋅ kg− ⋅ h−1) were slower than in controls. We conclude that 1) impaired reesterification, not accelerated lipolysis, elevates FFA in cirrhotic subjects; 2) normalized FFA after OLT masks impaired reesterification; and 3) plasma glycerol concentration poorly reflects lipolytic rate in cirrhosis and after OLT.