HEPATIC DE NOVO LIPOGENESIS AFTER LIVER TRANSPLANTATION

Kaori Minehira, Valérie Novel-Chaté, Jean-Marc Schwarz, Michel Gillet, Roger Darioli, René Chioléro, Luc Tappy
Institute of physiology, Lausanne University School of Medicine.

Background: The liver can synthesize fatty acids from carbohydrate (de novo lipogenesis : DNL).We hypothesized that stimulation of this process may be involved in the development of obesity and dyslipidemia, two conditions frequently encountered after liver transplantation.
Methods : Hepatic fractional DNL and glucose metabolism were measured in two groups of five patients (age 36.8 ± (SD) 14.9 y, BMI 26.3 ± 5.3 kg/m²) one to four years after liver transplantation and eight healthy subjects (age 28.1 ± 5.3 y, BMI 27.2 ± 4.5 kg/m²). Subjects were studied while receiving an isoenergetic nutrition (based on 1.1 * their basal energy expenditure) as hourly oral liquid formula during 10 hours. Their hepatic DNL was measured by infusing 1-¹³C acetate and measuring tracer incorporation in VLDL-palmitate. Their glucose metabolism was assessed by means of 6,6 ²H₂ glucose and indirect calorimetry.
Results : Two liver transplant recipients and four healthy subjects were obese, as defined by a BMI >27kg/m². Fractional hepatic DNL was not different in the two groups of subjects: liver transplant recipients 3.1 ± 1.7% vs 3.2 ± 2.1% in healthy subjects. In both groups, DNL increased in proportion to BMI. When both groups were analysed together, BMI was positively correlated with DNL (DNL = 0.278*BMI-4.262, r²= 0.445). Whole body glucose turnover was 15.0 ± 4.4 µmol/kg/min in liver transplant recipients and 15.8 ± 4.1 µmol/kg/min in healthy subjects (NS). Net carbohydrate oxidation tended to be lower in liver transplant recipients (8.1 ± 2.6 µmol/kg/min) than in healthy subjects (10.4 ± 2.4 µmol/kg/min; NS). Net non-oxidative glucose disposal (4.0 ± 2.7 in liver transplant recipients vs 1.9 ± 1.8 in healthy subjects, NS) and energy expenditure (0.065 ± 0.01 vs 0.065 ± 0.01 kJ/kg/min) were similar in both groups.
Conclusions : These results indicate that fractional hepatic DNL is not altered by liver transplantation during near continuous nutrition. The disposal of orally administered carbohydrate is also essentially unchanged. This strongly argue against a role of hepatic DNL in the pathogenesis of obesity and dyslipidemia after liver transplantation.